Nail dystrophy

Introduction A nail-to-sacral syndrome (nail-patellasyndrome) or hereditary bone-to-finger dystrophy (hereditary osteo-onyx dysplasia), a hereditary disease characterized by dysplasia or loss of the tibia (toe) nail dystrophy, elbow dysplasia, sacral horn and kidney failure.

Cause

In 1897, Little described the disease for the first time. In the mid-1960s, Muth and Silverman described the lesions of the glomerular structure of the syndrome. In the late 1960s and early 1970s, Hoyer and Bennett began a comprehensive study of the ultrastructure and renal pathological features of the glomerular basement membrane of this syndrome. A modern theory of the structural basis of renal lesions in this disease was proposed and suggested that the syndrome may be due to biochemical defects in the basement membrane collagen.

The disease is a hereditary disease and its transmission is autosomal dominant. The incidence rate is 4.5/1 million to 22/1 million, and there is no gender difference. The patient's chance of delivery to his offspring is 50%, and the locus is linked to the adenylate cyclase and ABO blood group sites on chromosome 9. Looij et al., based on their own data and data, concluded that if a patient with a family of the syndrome had significant clinical kidney performance, the risk of developing kidney disease in a child born to him was 1/4 health search, and the probability of developing renal failure was 1/10.

(1) Causes of the disease

The syndrome is autosomal dominant, and the locus is linked to the adenylate cyclase and ABO blood group on chromosome 9.

(two) pathogenesis

At present, little is known about the pathogenesis of this syndrome. Some people think that it is a collagen disease, and there are abnormalities in the process of collagen synthesis, assembly or degradation. The cytological mechanisms of this disease have not been studied. The lack of non-glomerular basement membrane damage in pathological changes suggests that the various damages in this syndrome may be due to different mechanisms, and not all lesions are associated with basement membrane abnormalities. A small number of patients developed anti-glomerular basement membrane nephritis, supporting the hypothesis that glomerular basement membrane components are abnormal. Using a monoclonal antibody against the Goodpasture epitope, it was found that the glomerular basement membrane of 2/3 patients with renal biopsy specimens did not bind to the monoclonal antibody, suggesting a basement membrane for this syndrome. There is some degree of heterogeneity in the components, which also suggests the presence of Goodpsture antigen deletion or alteration. It is worth noting that it is not clear whether this is a primary or secondary change in this syndrome.

an examination

Related inspection

Urine protein vitamin A vitamin A (VitA) serum complement C3 platelet-associated immunoglobulin (PAIgG, PAIgA, PAIgM)

1. Kidney performance

More than half of the nail-sacral syndrome patients had no significant clinical manifestations of the kidney. In patients with clinical renal manifestations, the characteristic manifestations are benign nephropathy. The most common symptoms are different degrees of proteinuria, microscopic hematuria and tubular urine, edema and hypertension. In one study, 56% of patients had abnormal deposits in the urine, impaired urinary concentration, abnormal uric acid or protein secretion. 30% of kidneys will develop slowly to kidney failure and die of uremia.

Meyrier et al. reported two families showing the diversity of progression of renal lesions. In one family, a 64-year-old male patient has a proteinuria that lasts for 20 years, with only mild insufficiency in his kidney function, and his brother died of kidney failure at the age of 25. One of the twin brothers of another family gradually developed into end-stage renal failure, while the other long-term only proteinuria. The literature shows that the degree of ultrastructural damage appears to have little to do with the severity and duration of clinical manifestations; the number of kidney stones is not equal to the number of congenital urinary tract malformations.

2. Skeletal and nail damage

The syndrome refers to abnormalities of the nails including discoloration, spoon-shaped nails, longitudinal tendons, finger nails or dystrophies, and triangular nail shadows. These manifestations are often symmetrical and exist in 80% to 90% of patients. Nail is more susceptible to nails and has the highest frequency of thumb involvement. About 60% of patients have humeral loss or dysplasia. These changes may be related to a reduction in the lateral side of the joint during flexion, which can lead to knee valgus deformity. Abnormal tibia can also lead to osteoarthritis, osteoarthrosis and joint effusion. 80% of patients with this syndrome have an open humerus, which protrudes forward and upward, called the humeral horn. Abnormal elbows include dysplasia and posterior processes of the distal radius, resulting in increased traction and extension, and limited supination. Individuals were associated with humeral head dysplasia and ankle joint abnormalities.

In the above manifestations, the loss of nails or hypoplasia, unilateral or bilateral humeral dysplasia or dysplasia, posterior tibial bone spurs, elbow and valgus valgus deformity, etc., are called nail-bone quadruple syndrome.

3. Other

In addition to glomerular basement membrane defects, radiological examination revealed other structural abnormalities in the kidney and urinary tract of the syndrome, including: pyelectasis and cortical scars, suggesting vesicoureteral reflux; unilateral nephrotic condensation and double ureter and double Renal pelvis; unilateral renal dysplasia and contralateral kidney; pyelone dull and kidney stones.

The main diagnosis of this disease is family history. The typical clinical manifestations are X-ray signs of bone and proteinuria. Renal biopsy is performed as necessary.

Clinically more common in adolescents, the main manifestations of kidney damage are proteinuria, microscopic hematuria, edema and hypertension, occasionally nephrotic syndrome, the course of the disease is relatively benign, only 10% of patients into the kidney failure. Extrarenal manifestations include nail dystrophies, absent bones on one or both sides, elbow deformities, angular pelvis, and other skeletal abnormalities. Most of the disease is caused by difficulty in walking due to lack of humerus. It can be diagnosed according to typical bone changes, and kidney damage can be diagnosed. Radiological examination showed that the humeral angle was a characteristic change and had a clear diagnostic significance.

It has been reported that a small number of patients have ultrastructural changes in the glomerular basement membrane without bones, skin, nails, and other typical manifestations of this syndrome. These patients are considered to be the frustration or single nephrotic variant of the syndrome. . However, the electron micrographs published by these institutes do not strongly support this view.

Judging the renal biopsy specimens can not only use the glomerular basement membrane moth, and the fibrils must be identified by phosphotungstic acid staining. Because of its higher sensitivity, it is more valuable for diagnosis.

There may be different degrees of proteinuria, microscopic hematuria and tubular urine, decreased urine concentration, abnormal uric acid or protein secretion. 30% of kidneys will develop slowly to renal failure, and there may be uremia changes in renal failure.

Light microscopy

The performance of glomeruli under light microscopy is quite variable. Patients without renal dysfunction usually have normal or near normal glomeruli. In some typical cases, partial capillary basement membrane thickening can be seen, but it is not ubiquitous. Global or focal glomerulosclerosis can also be seen, which is associated with the level of renal impairment, particularly the extent of proteinuria, suggesting a role for proteinuria in the progression of renal damage in this syndrome. Others may have epithelial cells and endothelial cells, accompanied by crescentic glomerular basement membrane disease, crescents, tubule atrophy and interstitial fibrosis parallel to the degree of renal dysfunction, arterial intimal fibrosis, arterioles Etc. At this time, it is often suggested that there is hypertension.

2. Immunofluorescence

Because the syndrome is not immune-mediated, glomerular immunohistochemistry results are often negative. In global or segmental glomerular sclerosis, irregular and focal deposition of IgM, C3, C1q, or all three can be observed. Sediments are distributed in the capillary wall or mesangial membrane or both, and their distribution is related to the stage and extent of glomerular sclerosis. Immunofluorescence may have a positive finding when concurrent with other pathological changes. In patients with concurrent glomerular basement membrane disease, IgG and C3 are linearly deposited in all glomerular capillaries, and fibrin deposition in capillaries is a manifestation of crescent formation. The link between this syndrome and anti-glomerular basement membrane disease is unclear. It may be that the glomerular basement membrane of patients with nail-to-sacral syndrome continues and severely damages the antigen of the glomerular basement membrane. Sex, leading to antibody production. Mackay et al reported a case of nail-sacral syndrome with membranous glomerulonephritis, showing uniform granular IgG deposition on all capillary walls.

3. Ultrastructure

Regardless of the glomerular manifestations under light microscopy in patients with this syndrome, and regardless of the presence of renal symptoms such as proteinuria in the clinic, the ultrastructure of the glomerular basement membrane is altered.

Common and characteristic lesions are ultrastructural abnormalities of the glomerular basement membrane, and a large number of patchy translucent substances are seen in the whole layer of the basement membrane. This kind of thing is sometimes seen in the mesangial matrix, which is called Characteristic "moth" performance. Dyeing with standard lead citrate sometimes results in coarse fibrils and cross-banded collagen in the glomerular basement membrane and mesangial matrix. The above substances are more common when dyed with phosphotungstic acid. The fibrils are small clusters, localized in the basal ganglia, or distributed along the entire glomerular basement membrane. The thickness of the glomerular basement membrane is not uniform, and the thickness of the glomerular basement wall can vary from normal to thick. In the thickened part of the glomerular basement membrane, the translucent band is more and more prominent. The glomerular mesangial matrix is also increased, and in some cases, translucent substances and collagen fibers are seen. The non-small basement membrane of the kidney is free of translucent and collagen-like fibrils, and the changes of the basement membrane of the renal tubule are chronic tubulointerstitial nephropathy-like lesions, which are consistent with glomerular damage in the late stage.

In most cases, there is no electron dense deposit. The glomerular visceral epithelial cells often decrease or disappear, and the degree of reduction is related to the severity of proteinuria.

Common vesicoureteral reflux; renal pelvis becomes dull and kidney stones, posterior tibial bone spurs, elbow and humeral deformity, etc., even with iris pigment abnormalities.

Differential diagnosis

Differential diagnosis of nail dystrophies:

1. The nails become soft or deformed: the nails become soft and deformed, which is the clinical manifestation of hyperthyroidism.

2, nail dryness: nails due to a variety of factors, the appearance of dry symptoms of clinical manifestations. Abnormal nails, diabetic peripheral neuropathy, nail malnutrition and other diseases can cause nails to dry up. A includes the deck, the nail bed and the nail week. Fingernail abnormalities involve the above three parts. The factors that cause nail lesions are classified as congenital or acquired. Congenital nail lesions often associated with other congenital anomalies. Acquired nail lesions are found in microbial infections and local factors. Abnormal changes in nails caused by systemic diseases or certain skin diseases. There may also be damage to the original nail for unknown reasons.

3, the fingertip edge of the nail has a depression: the fingertip edge of the nail has a depression refers to the fingertip edge of the nail appears concave.

4, the nails appear black: the nails are black, the nails appear black, suggesting that endocrine disorders, such symptoms can also occur for a long time.

5. Nail abnormalities: A includes deck, nail bed and nail week. Fingernail abnormalities involve the above three parts. The factors that cause nail lesions are classified as congenital or acquired. Congenital nail lesions often associated with other congenital anomalies. Acquired nail lesions are found in microbial infections and local factors. Abnormal changes in nails caused by systemic diseases or certain skin diseases. There may also be damage to the original nail for unknown reasons.

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