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AS has an insidious onset, and patients develop pain and/or stiffness in the lower back or sacroiliac region gradually, which decreases
with activity.
Some patients have dull hip pain or severe lumbosacral pain that occasionally radiates
to the periphery.
Most patients with AS develop from the lumbar spine to the thoracic and cervical spine, with pain, limited mobility, or spinal deformities
.
• Laboratory findings for AS are generally non-specific
.
• 50%~70% of patients with active AS may have elevated inflammatory indicators in the acute phase, including elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
• Rheumatoid factor (RF) is mostly negative, but a positive RF does not exclude the diagnosis
of AS.
• HLA-B27 is not diagnostic specific
.
HLA-B27 negative patients cannot rule out AS as long as the clinical manifestations and imaging tests meet the AS classification criteria
.
Diagnostic testing
● Sacroiliac joint and paravertebral muscle tenderness are positive signs
in the early stages of AS.
● Several methods can be used to check for sacroiliac joint tenderness or spinal progression: occipital wall test, thoracic extension, Schober test, pelvic compression, Patrick test (lower extremity "4" test).
● X-ray changes in the sacroiliac joint are diagnostic
.
Sacroiliitis on x-ray shows blurred subchondral margins, bone erosions, blurred joint spaces, increased bone density, and joint fusion
.
● Pelvic X-ray can also show bone erosion (enthesitis) of pubic symphysis and ischial tubercles, accompanied by reactive sclerosis and villiform changes in adjacent bones, and new bone formation
may occur.
● Spinal X-ray showed vertebral osteoporosis and square degeneration, blurred vertebral facet joints, paravertebral ligament calcification and bone bridge formation
.
Late manifestations have extensive and severe symmetrical bony bone bridges called "bamboo spines"
.
● High-resolution CT shows structural changes in the sacroiliac joint, such as erosion, sclerosis, and rigidity
, more clearly than x-rays.
● Unlike x-rays and CT, sacroiliac joint MRI can show acute inflammatory changes and structural damage changes, resulting in earlier detection of sacroiliac joint lesions
in patients with SpA 。 MRI mainly selects water-sensitive sequences, including short-term inversion recovery sequence (STIR) or T2-weighted fat suppression sequence (T2FS), to assess sacroiliac joint activity for the presence of myeloedema, bursitis, tendonitis, and interjoint fluid; Evaluation of structural changes requires attention to the T1WI sequence for bone erosion, fat infiltration, backfilling, sclerosis, bone buds, and rigidity
.
Fat infiltration is specific for the diagnosis of SpA, and the presence of fat infiltration with bone erosion or bone marrow edema improves diagnostic accuracy
.
The diagnostic criteria
for classification are still based on the AS New York criteria
revised in 1984 。 For some who do not meet the above criteria temporarily, you can refer to the relevant SpA classification standards, mainly including Amor, the European Spondyloarthropathy Research Group (ESSG) and the axial SpA classification standard
developed by ASAS in 2009.
(1) NSAIDs
● can rapidly improve low back pain and morning stiffness in AS patients, reduce joint swelling and pain and increase range of motion, and are the first choice for symptomatic treatment of early or late AS patients.
● Physicians should select one NSAIDs for each patient's specific situation, usually the maximum dose
.
● To assess whether a particular NSAIDs are effective, a stable dose should be used regularly for at least 2 weeks
.
● If the efficacy of 1 NSAIDs is not obvious for 2~4 weeks, other different types of NSAIDs
should be used.
● Regardless of the NSAIDs used, it is generally recommended to continue their use for a longer period of time at current drug doses in order to improve symptoms and to delay or control disease progression.
● Adverse drug reactions should be monitored and adjusted
in time during medication.
(2) Biological DMARDs
)
have not been proved to be effective
for axial lesions of AS 。 If more effective treatment is not available to clinicians and patients, traditional synthetic DMARDs
can be tried.
(1) Sulfasalazine
(2) Thalidomide
(3) Methotrexate, leflunomide, ellamod and anti-rheumatic botanicals can be used to treat patients with peripheral joint involvement in AS, but their efficacy on axial joint lesions is uncertain and further research
is needed.
Figure 4: Key points for the use of traditional synthetic DMARDs
When patients with AS have limited function or joint deformities that significantly affect quality of life, such as severe kyphosis of the cervicothoracic segment, severe progressive thoracic kyphosis with loss of heads-up ability, refractory and persistent hip pain, or hip ankylosis in a non-functional position, and adequate medical treatment cannot effectively alleviate the condition, cervical-thoracic orthopedics, thoracolumbar orthopedics, or hip replacement surgery
may be considered.
Spinal fixation surgery
may be considered in patients with AS with acute spinal fractures.
References: [1] HUANG F, ZHU Jian, WANG Yuhua, et al Norms for the diagnosis and treatment of ankylosing spondylitis[J].
Chinese Journal of Internal Medicine, 2022, 61(8): 893-900.
DOI:10.
3760/cma.
j.
cn112138-20211226-00913
~
Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly invades the sacroiliac joint, spine, paraspinal soft tissues and peripheral joints, and can be accompanied by extra-articular manifestations, and spinal deformity and rigidity
can occur in severe cases.
Recently, the Rheumatology Branch of the Chinese Medical Association formulated this code [1] on the basis of drawing on domestic and foreign experience and treatment experience and guidelines, aiming to standardize the diagnosis and condition assessment of AS, rationally use nonsteroidal anti-inflammatory drugs (NSAIDs), biological and traditional synthetic antirheumatic drugs (DMARDs), and improve the quality of
life of patients.
What exactly does the guide say? Let's take a look with the editor~
Besides inflammatory back pain, what are the other symptoms?
AS has an insidious onset, and patients develop pain and/or stiffness in the lower back or sacroiliac region gradually, which decreases
with activity.
Some patients have dull hip pain or severe lumbosacral pain that occasionally radiates
to the periphery.
Most patients with AS develop from the lumbar spine to the thoracic and cervical spine, with pain, limited mobility, or spinal deformities
.
- Low back pain is a very common symptom in the general population, but most of them are mechanical
, while AS is inflammatory back pain
.
Table 1: Diagnostic criteria for inflammatory back pain recommended by the 2009 ASAS Panel of Experts on Inflammatory Back Pain
Enthesitis is a classic feature of AS and presents with pain, stiffness, and tenderness at the attachment site, usually without significant swelling
.
Peripheral joint involvement is a common extraspinal manifestation of AS, with asymmetric joint swelling, pain, and limited
mobility, mainly the lower extremities.
- Extraarticular manifestations of AS include anterior uveitis, psoriasis and inflammatory bowel disease, neurologic symptoms, upper lobe fibrosis, aortic regurgitation and conduction disorders, renal amyloidosis, and IgA-related nephropathy
.
X-ray, CT or MRI?
• Laboratory findings for AS are generally non-specific
.
• 50%~70% of patients with active AS may have elevated inflammatory indicators in the acute phase, including elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
• Rheumatoid factor (RF) is mostly negative, but a positive RF does not exclude the diagnosis
of AS.
• HLA-B27 is not diagnostic specific
.
HLA-B27 negative patients cannot rule out AS as long as the clinical manifestations and imaging tests meet the AS classification criteria
.
Diagnostic testing
● Sacroiliac joint and paravertebral muscle tenderness are positive signs
in the early stages of AS.
● Several methods can be used to check for sacroiliac joint tenderness or spinal progression: occipital wall test, thoracic extension, Schober test, pelvic compression, Patrick test (lower extremity "4" test).
● X-ray changes in the sacroiliac joint are diagnostic
.
Sacroiliitis on x-ray shows blurred subchondral margins, bone erosions, blurred joint spaces, increased bone density, and joint fusion
.
● Pelvic X-ray can also show bone erosion (enthesitis) of pubic symphysis and ischial tubercles, accompanied by reactive sclerosis and villiform changes in adjacent bones, and new bone formation
may occur.
● Spinal X-ray showed vertebral osteoporosis and square degeneration, blurred vertebral facet joints, paravertebral ligament calcification and bone bridge formation
.
Late manifestations have extensive and severe symmetrical bony bone bridges called "bamboo spines"
.
● High-resolution CT shows structural changes in the sacroiliac joint, such as erosion, sclerosis, and rigidity
, more clearly than x-rays.
● Unlike x-rays and CT, sacroiliac joint MRI can show acute inflammatory changes and structural damage changes, resulting in earlier detection of sacroiliac joint lesions
in patients with SpA 。 MRI mainly selects water-sensitive sequences, including short-term inversion recovery sequence (STIR) or T2-weighted fat suppression sequence (T2FS), to assess sacroiliac joint activity for the presence of myeloedema, bursitis, tendonitis, and interjoint fluid; Evaluation of structural changes requires attention to the T1WI sequence for bone erosion, fat infiltration, backfilling, sclerosis, bone buds, and rigidity
.
Fat infiltration is specific for the diagnosis of SpA, and the presence of fat infiltration with bone erosion or bone marrow edema improves diagnostic accuracy
.
The diagnostic criteria
for classification are still based on the AS New York criteria
revised in 1984 。 For some who do not meet the above criteria temporarily, you can refer to the relevant SpA classification standards, mainly including Amor, the European Spondyloarthropathy Research Group (ESSG) and the axial SpA classification standard
developed by ASAS in 2009.
Table 2: AS New York Standard revised in 1984
3 major treatments
01.
Non-drug treatment
02.
Drug treatment
(1) NSAIDs
● can rapidly improve low back pain and morning stiffness in AS patients, reduce joint swelling and pain and increase range of motion, and are the first choice for symptomatic treatment of early or late AS patients.
● Physicians should select one NSAIDs for each patient's specific situation, usually the maximum dose
.
● To assess whether a particular NSAIDs are effective, a stable dose should be used regularly for at least 2 weeks
.
● If the efficacy of 1 NSAIDs is not obvious for 2~4 weeks, other different types of NSAIDs
should be used.
● Regardless of the NSAIDs used, it is generally recommended to continue their use for a longer period of time at current drug doses in order to improve symptoms and to delay or control disease progression.
● Adverse drug reactions should be monitored and adjusted
in time during medication.
Figure 2: Key points of NSAIDs medication
(2) Biological DMARDs
- Biologic DMARDs should be considered in patients with AS who remain active despite NSAIDs, and current drug options include tumor necrosis factor (TNF) α inhibitors and interleukin (IL)-17 inhibitors
.
- Recommended timing of bio-DMARDs: treatment with at least 2 NSAIDs for more than 4 weeks with persistent symptom relief and / or adverse reactions, ASDAS≥2.
1 or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4
.
- Screening for tuberculosis, hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) (in high-risk populations) is required prior to initiation of treatment with biologic DMARDs, treatment of latent TB, and prophylactic treatment of chronic hepatitis B virus infection
.
- Patients with AS who have undergone treatment with one biological DMARDs for at least 12 weeks should have responded to
treatment by assessing changes in mobility.
Using the same outcome measure (ASDAS or BASDAI) to define treatment response, clinically meaningful improvement was ΔASDAS≥1.
1 or ΔBASDAI≥2.
0
.
If these changes are not achieved, the potential risks and benefits should be considered, and the decision to continue treatment with biologic DMARDs should be made with the patient
.
- If one TNF inhibitor fails, consideration should be given to switching to another TNF inhibitor or IL-17 inhibitor
.
Until then, the correct indications for treatment with the first TNF inhibitor must be
reassessed.
- If the patient remains in remission, tapering of biological DMARDs may be considered
.
Complete discontinuation of biologic DMARDs may result in a high proportion of disease relapse, so tapering should be done very slowly and sufficient time to maintain remission
after the previous tapering.
Figure 3: Key points of use of biologics DMARDs
(3) Traditional synthetic DMARDs (such as methotrexate, leflunomide, sulfasalazine, etc.)
have not been proved to be effective
for axial lesions of AS 。 If more effective treatment is not available to clinicians and patients, traditional synthetic DMARDs
can be tried.
(1) Sulfasalazine
- May improve joint pain, swelling, and stiffness in AS, and reduce serum IgA levels and other markers of mobility
(e.
g.
, ESR, CRP), especially for improving peripheral arthritis
in AS patients.
- The recommended dosage is 2.
0 g per day, divided into 2~3 oral administrations
.
The dose was increased to 3.
0 g/d, and although the efficacy could be increased, the adverse reactions were also significantly increased
.
- Sulfasalazine has a slow onset of action, usually 4~6 weeks after medication
.
- To increase patient tolerability, generally start with 0.
25 g three times a day, and then increase by 0.
25 g weekly until 2 g daily, and the dose and course can also be adjusted according to the condition or the patient's response to treatment.
Maintain for 1~3 years
.
- Due to the shortcomings of sulfasalazine with slow onset and weak anti-inflammatory effect, one NSAIDs with fast onset is usually used in combination with it
.
- Adverse effects include digestive symptoms, rash, cytopenias, headache, dizziness, male spermatozoa, and morphological abnormalities (which can be recovered with discontinuation of the drug
).
Patients allergic to sulfonamides are banned
.
(2) Thalidomide
- Thalidomide significantly improves clinical symptoms, ESR, and CRP
in some men with refractory AS.
- The initial dose is 50mg/night, and it is increased by 50 mg every 10~14 days to 150~200 mg/night to maintain
.
If the dosage is insufficient, the effect is not good, and the symptoms can quickly recur
after stopping the drug.
- The adverse reactions of thalidomide include drowsiness, thirst, decreased blood cells, increased liver enzymes, microscopic hematuria and tingling sensation in the fingertips
.
Therefore, blood routine, urine routine, liver function, and kidney function
should be regularly checked in the early stage of medication.
For long-term users, regular neurological examination should be done to detect possible peripheral neuritis
in time.
(3) Methotrexate, leflunomide, ellamod and anti-rheumatic botanicals can be used to treat patients with peripheral joint involvement in AS, but their efficacy on axial joint lesions is uncertain and further research
is needed.
Figure 4: Key points for the use of traditional synthetic DMARDs
(4) Glucocorticoids (hereinafter referred to as hormones).
Figure 5: Key points for glucocorticoid use
03.
Surgical treatment
When patients with AS have limited function or joint deformities that significantly affect quality of life, such as severe kyphosis of the cervicothoracic segment, severe progressive thoracic kyphosis with loss of heads-up ability, refractory and persistent hip pain, or hip ankylosis in a non-functional position, and adequate medical treatment cannot effectively alleviate the condition, cervical-thoracic orthopedics, thoracolumbar orthopedics, or hip replacement surgery
may be considered.
Spinal fixation surgery
may be considered in patients with AS with acute spinal fractures.
References: [1] HUANG F, ZHU Jian, WANG Yuhua, et al Norms for the diagnosis and treatment of ankylosing spondylitis[J].
Chinese Journal of Internal Medicine, 2022, 61(8): 893-900.
DOI:10.
3760/cma.
j.
cn112138-20211226-00913
