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*Only for medical professionals to read and refer is really full of dry goods~
For rheumatology and
immunology, Acral discoloration is a very common symptom, according to which it is also necessary to distinguish between vasculopathy and vasculitis, and the 2022 American College of Rheumatology (ACR) Annual Meeting details how to make a differential diagnosis
based on the discolored finger (toe) from the most common digital ischemia of vascular lesions and vasculitis.
The "Rheumatology and Immunology Channel of the Medical Community" invited Professor Liu Yanying of Beijing Friendship Hospital to share the common acral discoloration in simple terms through the live broadcast interpretation activity of "Youth Committee of the Rheumatology Society Take You to See ACR".
Causes of
ischemia
The causes of digital ischemia are mainly cardiovascular diseases, rheumatism, idiopathic and blood diseases [1], of which:
Figure 1.
Common causes
of acral ischemia refer to the differential diagnosis
of (toe) ischemia
In general, when clinical suspicion of discoloration of the fingers (toes) due to limb ischemia is encountered, acute phase reaction markers such as erythrocyte sedimentation rate (ESR) should be screened first, and the test results should be preliminarily judged whether it is vascular disease or vasculitis
.
Reynolds manifests itself as the phenomenon of "finger (toe) asphyxiation" proposed by Dr.
Reynolds in 1862, characterized by episodic "three-phase" changes - that is, pallor, cyanosis, flushing
.
Raynaud's can usually be caused by cold exposure, emotional triggers (eg, stress, anxiety), and can be divided into
primary Raynaud's disease, which must be bilateral and have no secondary cause for at least 2 years; The age of onset is usually 15 to 40 years; Female male prevalence 4-8:1; 15% spontaneous improvement, 30% progression; Ulcers are rare; <1% of patients lose part of the fingers (toes).
Secondary, Raynaud's syndrome, secondary to connective tissue disease, arterial occlusive disease, thoracic outlet syndrome, heat or vibration trauma, cachexia, neurological disease, use of vasoconstrictors, chemotherapy, etc.
, the course of the disease is related
to the cause.
However, Raynaud's performance also needs to be distinguished from other conditions, and the main points are whether there is a three-phase change and whether it is cold or emotionally induced
.
As shown in the figure below: The figure on the right shows spontaneous venous bleeding
from the fingers (toes).
If Raynaud's manifestations are present, the first thing to consider is the presence of secondary factors such as cardiogenic factors, antiphospholipid syndrome, small fish hammering syndrome, thromboangiitis obliterans, and digital ischemia
due to other causes (cannabis-associated arteritis, direct vascular injury, drug injection).
The identification of ischemia at the finger (toe) end is mainly considered from the following aspects: atheroembolism:
a variety of clinical manifestations can be seen, among which the skin is purple / blue finger (toe), finger (toe) gangrene, reticular bruis, nodules;
Renal manifestations of uncontrollable hypertension and renal failure;
Neurological manifestations include transient ischemic attack, transient amaurosis, stroke, Hollenhorst spots;
Cardiac manifestations of myocardial infarction or myocardial ischemia;
Gastrointestinal manifestations include abdominal pain, gastrointestinal bleeding, mesenteric ischemic disease, acute pancreatitis;
Constitutional symptoms (fever, weight loss, anorexia, etc.
) may also be seen
.
In general, severe and diffuse atherosclerosis has a poor prognosis, with mortality rates ranging from 64% to 81%, causes of death including myocardial infarction, stroke, and mesenteric ischemia, atherosclerosis can be confused with a variety of conditions, especially necrotizing vasculitis, and screening for coronary arteries and extracranial carotid arteries is helpful
.
Livedo reticularis:
Manifested as marble-like skin, divided into primary and secondary, secondary causes generally include antiphospholipid syndrome, cutaneous vasculitis, cryoglobulinemia, vascular calcification, amantadine use, etc
.
Chilblains:
generally due to the abnormal reaction of the extremities to cold, which leads to local inflammatory lesions of the skin, is a vasospastic disease caused by cold, and needs to be distinguished from the rapid reversible vasospasm manifested by Raynaud, generally the vasospasm caused by chilblain has a long course, It usually starts in winter and ends
in spring.
Thromboangiitis
obliterans: (Berg disease) has 2 diagnostic criteria, namely Shionoyal Criteria (smoking history; Age of onset less than 50 years; Occlusion of the inferior knee artery; Arm vascular involvement or migratory phlebitis; There are no risk factors for atherosclerosis other than smoking) and Olin criteria (age younger than 45 Year; a history of current or recent tobacco use; Noninvasive vascular examination confirms distal lower extremity ischaemia: claudication, rest pain, ischaemic ulcers, or gangrene; exclude definitive autoimmune disease, hypercoagulability, and diabetes mellitus; echocardiography or arteriography to exclude emboli of proximal origin; Clinically affected and non-affected limb arteriogram findings are consistent).
There have been no case reports of people who do not smoke (cigarettes, cigars, pipes) or use any other form of tobacco (chewing, snus, etc.
), and cannabis-associated arteritis is a subtype of Berg disease, which is the same
as excessive smoking.
Therefore, patients with suspected disease should undergo urine toxicology screening, and cocaine and amphetamine-related vasculitis can present similarly in addition to cannabis
.
If the antastropic reactant is elevated acutely, the cause of digital ischaemia should be considered:
subclavian artery stenosis is usually seen in macrovasculitis (LVV), and LVV-associated subclavian artery stenosis is not a common cause
of finger ischemia.
Because LVV is a subacute disease, collateral circulation compensates for proximal vascular stenosis, and patients with symptoms of upper extremity ischemia can be evaluated
by CTA.
Middle vasculitis (polyarteritis nodosa) is often manifested by CTA abnormalities (renal infarction, visceral aneurysm), skin ulcers (similar to pyoderma gangrenosum), neurologic involvement (mononeuritis multiplex, length-dependent sensory neuropathy), and testicular infarction (ultrasound), while limb angiography and biopsy are less
clinical.
In addition, polyarteritis nodosa + rheumatoid arthritis≈ rheumatoid vasculitis (no microaneurysm), may be combined with limb manifestations (skin ulcers, mononeuritis multiplex), other manifestations (corneal ulcers are more common, but cardiovascular/lung/kidney/gastrointestinal manifestations are uncommon), positive rheumatoid factor/anti-cyclic citrullinated antibodies, and chronic bone erosion
on imaging.
Small vessel vasculitis (SVV) is also usually not a common cause of (toe) ischemia, SVV conditions need to be considered, including purpura, pulmonary hemorrhage, glomerulonephritis, etc.
, different clinical phenotypes of SVV-specific diagnosis basis is different, such as granulomatosis polyangiitis ANCA positive, chronic sinusitis, etc.
, and cryoglobulin vasculitis rheumatoid factor positive, while C4 is low, C3 is normal
。
The etiology of digital (toe) ischemia is complex, often related to peripheral vascular disease, and most of them are not caused by rheumatism, so clinical attention should be paid to differential diagnosis
.
Although vasculitis is not a common cause of ischemia, it must be carefully differentiated during diagnosis
.
Among them, macrovasculitis can be fully excluded by CTA; Patients should also undergo a clinical evaluation for evidence of small vessel vasculitis; Clinical diagnosis of polyarteritis nodosa and rheumatoid vasculitis is relatively difficult because biopsy diagnosis is often unconfirmable, and it is important to distinguish endocarditis (which can present with many of the confounding symptoms of mesovasculitis when looking for evidence of vascular involvement in other systems).
Expert profiles
References: [1] Grayson P C, Carmona-Rivera C, Xu L, et al.
Neutrophil‐related gene expression and low‐density granulocytes associated with disease activity and response to treatment in antineutrophil cytoplasmic antibody–associated vasculitis[J].
Arthritis & rheumatology, 2015, 67(7): 1922-1932.
[2]Rhee R L, Lu J, Bittinger K, et al.
Dynamic changes in the nasal microbiome associated with disease activity in patients with granulomatosis with polyangiitis[J].
Arthritis & Rheumatology, 2021, 73(9): 1703-1712.
[3]Abreu N A, Nagalingam N A, Song Y, et al.
Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis[J].
Science translational medicine, 2012, 4(151): 151ra124-151ra124.
[4]Jaiswal S, Fontanillas P, Flannick J, et al.
Age-related clonal hematopoiesis associated with adverse outcomes[J].
New England Journal of Medicine, 2014, 371(26): 2488-2498.
[5]Jaiswal S, Natarajan P, Silver A J, et al.
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease[J].
New England Journal of Medicine, 2017, 377(2): 111-121.
For rheumatology and
immunology, Acral discoloration is a very common symptom, according to which it is also necessary to distinguish between vasculopathy and vasculitis, and the 2022 American College of Rheumatology (ACR) Annual Meeting details how to make a differential diagnosis
based on the discolored finger (toe) from the most common digital ischemia of vascular lesions and vasculitis.
The "Rheumatology and Immunology Channel of the Medical Community" invited Professor Liu Yanying of Beijing Friendship Hospital to share the common acral discoloration in simple terms through the live broadcast interpretation activity of "Youth Committee of the Rheumatology Society Take You to See ACR".
Causes of
ischemia
The causes of digital ischemia are mainly cardiovascular diseases, rheumatism, idiopathic and blood diseases [1], of which:
•Cardiovascular causes include cardiac embolism (41 percent), iatrogenic causes (20 percent, interventional surgery, puncture, etc.
), atherosclerosis (7 percent), thoracic outlet syndrome (6 percent ), trauma (6%), and others, such as infections (sepsis, endocarditis), vascular factors (vasospasm), hypotension, frostbite, calcifications, etc
.
•Causes of hematologic disorders include malignancy (63 percent), antiphospholipid syndrome (23 percent), and other causes (9 percent) such as hypercoagulable states, disseminated intravascular coagulation, and cold agglutinin disease
.
•Rheumatological causes included scleroderma (51 percent), thromboangiitis obliterans (29 percent), antiphospholipid syndrome (6 percent), and primary systemic vasculitis (10 percent).
and secondary vasculitis such as systemic lupus erythematosus (1%), Sjogren's syndrome (1%), dermatomyositis (1%), and undifferentiated connective tissue disease (1%)
。
Figure 1.
Common causes
of acral ischemia refer to the differential diagnosis
of (toe) ischemia
In general, when clinical suspicion of discoloration of the fingers (toes) due to limb ischemia is encountered, acute phase reaction markers such as erythrocyte sedimentation rate (ESR) should be screened first, and the test results should be preliminarily judged whether it is vascular disease or vasculitis
.
Reynolds manifests itself as the phenomenon of "finger (toe) asphyxiation" proposed by Dr.
Reynolds in 1862, characterized by episodic "three-phase" changes - that is, pallor, cyanosis, flushing
.
Raynaud's can usually be caused by cold exposure, emotional triggers (eg, stress, anxiety), and can be divided into
primary Raynaud's disease, which must be bilateral and have no secondary cause for at least 2 years; The age of onset is usually 15 to 40 years; Female male prevalence 4-8:1; 15% spontaneous improvement, 30% progression; Ulcers are rare; <1% of patients lose part of the fingers (toes).
Secondary, Raynaud's syndrome, secondary to connective tissue disease, arterial occlusive disease, thoracic outlet syndrome, heat or vibration trauma, cachexia, neurological disease, use of vasoconstrictors, chemotherapy, etc.
, the course of the disease is related
to the cause.
However, Raynaud's performance also needs to be distinguished from other conditions, and the main points are whether there is a three-phase change and whether it is cold or emotionally induced
.
As shown in the figure below: The figure on the right shows spontaneous venous bleeding
from the fingers (toes).
Figure 2.
Reynolds on the left and spontaneous subcutaneous hemorrhage on the right
If Raynaud's manifestations are present, the first thing to consider is the presence of secondary factors such as cardiogenic factors, antiphospholipid syndrome, small fish hammering syndrome, thromboangiitis obliterans, and digital ischemia
due to other causes (cannabis-associated arteritis, direct vascular injury, drug injection).
The identification of ischemia at the finger (toe) end is mainly considered from the following aspects: atheroembolism:
a variety of clinical manifestations can be seen, among which the skin is purple / blue finger (toe), finger (toe) gangrene, reticular bruis, nodules;
Renal manifestations of uncontrollable hypertension and renal failure;
Neurological manifestations include transient ischemic attack, transient amaurosis, stroke, Hollenhorst spots;
Cardiac manifestations of myocardial infarction or myocardial ischemia;
Gastrointestinal manifestations include abdominal pain, gastrointestinal bleeding, mesenteric ischemic disease, acute pancreatitis;
Constitutional symptoms (fever, weight loss, anorexia, etc.
) may also be seen
.
In general, severe and diffuse atherosclerosis has a poor prognosis, with mortality rates ranging from 64% to 81%, causes of death including myocardial infarction, stroke, and mesenteric ischemia, atherosclerosis can be confused with a variety of conditions, especially necrotizing vasculitis, and screening for coronary arteries and extracranial carotid arteries is helpful
.
Livedo reticularis:
Manifested as marble-like skin, divided into primary and secondary, secondary causes generally include antiphospholipid syndrome, cutaneous vasculitis, cryoglobulinemia, vascular calcification, amantadine use, etc
.
Chilblains:
generally due to the abnormal reaction of the extremities to cold, which leads to local inflammatory lesions of the skin, is a vasospastic disease caused by cold, and needs to be distinguished from the rapid reversible vasospasm manifested by Raynaud, generally the vasospasm caused by chilblain has a long course, It usually starts in winter and ends
in spring.
Thromboangiitis
obliterans: (Berg disease) has 2 diagnostic criteria, namely Shionoyal Criteria (smoking history; Age of onset less than 50 years; Occlusion of the inferior knee artery; Arm vascular involvement or migratory phlebitis; There are no risk factors for atherosclerosis other than smoking) and Olin criteria (age younger than 45 Year; a history of current or recent tobacco use; Noninvasive vascular examination confirms distal lower extremity ischaemia: claudication, rest pain, ischaemic ulcers, or gangrene; exclude definitive autoimmune disease, hypercoagulability, and diabetes mellitus; echocardiography or arteriography to exclude emboli of proximal origin; Clinically affected and non-affected limb arteriogram findings are consistent).
There have been no case reports of people who do not smoke (cigarettes, cigars, pipes) or use any other form of tobacco (chewing, snus, etc.
), and cannabis-associated arteritis is a subtype of Berg disease, which is the same
as excessive smoking.
Therefore, patients with suspected disease should undergo urine toxicology screening, and cocaine and amphetamine-related vasculitis can present similarly in addition to cannabis
.
Figure 3.
Digital ischemia caused by different etiologies (A: atheroembolism; B: livedo reticularis; C&D: chilblas; E&F: thromboangiitis obliterans)
If the antastropic reactant is elevated acutely, the cause of digital ischaemia should be considered:
subclavian artery stenosis is usually seen in macrovasculitis (LVV), and LVV-associated subclavian artery stenosis is not a common cause
of finger ischemia.
Because LVV is a subacute disease, collateral circulation compensates for proximal vascular stenosis, and patients with symptoms of upper extremity ischemia can be evaluated
by CTA.
Middle vasculitis (polyarteritis nodosa) is often manifested by CTA abnormalities (renal infarction, visceral aneurysm), skin ulcers (similar to pyoderma gangrenosum), neurologic involvement (mononeuritis multiplex, length-dependent sensory neuropathy), and testicular infarction (ultrasound), while limb angiography and biopsy are less
clinical.
In addition, polyarteritis nodosa + rheumatoid arthritis≈ rheumatoid vasculitis (no microaneurysm), may be combined with limb manifestations (skin ulcers, mononeuritis multiplex), other manifestations (corneal ulcers are more common, but cardiovascular/lung/kidney/gastrointestinal manifestations are uncommon), positive rheumatoid factor/anti-cyclic citrullinated antibodies, and chronic bone erosion
on imaging.
Small vessel vasculitis (SVV) is also usually not a common cause of (toe) ischemia, SVV conditions need to be considered, including purpura, pulmonary hemorrhage, glomerulonephritis, etc.
, different clinical phenotypes of SVV-specific diagnosis basis is different, such as granulomatosis polyangiitis ANCA positive, chronic sinusitis, etc.
, and cryoglobulin vasculitis rheumatoid factor positive, while C4 is low, C3 is normal
。
Figure 4.
Vasculitis classification
summary
The etiology of digital (toe) ischemia is complex, often related to peripheral vascular disease, and most of them are not caused by rheumatism, so clinical attention should be paid to differential diagnosis
.
Although vasculitis is not a common cause of ischemia, it must be carefully differentiated during diagnosis
.
Among them, macrovasculitis can be fully excluded by CTA; Patients should also undergo a clinical evaluation for evidence of small vessel vasculitis; Clinical diagnosis of polyarteritis nodosa and rheumatoid vasculitis is relatively difficult because biopsy diagnosis is often unconfirmable, and it is important to distinguish endocarditis (which can present with many of the confounding symptoms of mesovasculitis when looking for evidence of vascular involvement in other systems).
Figure 5.
Refers to the thought flow of differential diagnosis of ischemia
Expert profiles
Professor Liu Yanying
•Chief physician, professor, doctoral supervisor
• Ph.
D.
, Peking University Health Science Center
• Postdoctoral fellow at Karolinska University, Sweden
•Youth Committee of Rheumatology Branch of Chinese Medical Association
•Youth Committee Member of Rheumatology and Immunologist Branch of Chinese Medical Doctor Association
•Member of the Standing Committee and Secretary-General of the IgG4-related Disease Group of the Cross-Strait Medical and Health Association
•Member of the Standing Committee and Deputy Secretary-General of the Immunopurification and Cell Therapy Group of the Internal Medicine Branch of the Chinese Medical Association
•Specially appointed expert of the National Physician Regular Assessment of Chinese Medical Doctor Association
•He has presided over 9 projects including the National Key Research and Development Program (sub-project) of the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Doctoral Program Fund of the Ministry of Education
•Published 71 articles in Chinese and English, including 41 articles by the first author or corresponding author
References: [1] Grayson P C, Carmona-Rivera C, Xu L, et al.
Neutrophil‐related gene expression and low‐density granulocytes associated with disease activity and response to treatment in antineutrophil cytoplasmic antibody–associated vasculitis[J].
Arthritis & rheumatology, 2015, 67(7): 1922-1932.
[2]Rhee R L, Lu J, Bittinger K, et al.
Dynamic changes in the nasal microbiome associated with disease activity in patients with granulomatosis with polyangiitis[J].
Arthritis & Rheumatology, 2021, 73(9): 1703-1712.
[3]Abreu N A, Nagalingam N A, Song Y, et al.
Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis[J].
Science translational medicine, 2012, 4(151): 151ra124-151ra124.
[4]Jaiswal S, Fontanillas P, Flannick J, et al.
Age-related clonal hematopoiesis associated with adverse outcomes[J].
New England Journal of Medicine, 2014, 371(26): 2488-2498.
[5]Jaiswal S, Natarajan P, Silver A J, et al.
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease[J].
New England Journal of Medicine, 2017, 377(2): 111-121.
