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Flashcards in Rheumatology Deck (35)
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1
Q

Sensitivity

A

percentage of individuals with the condition that the test identifies.

2
Q

Specificity

A

Percentage of individuals who do not have the condition that the test excludes.

3
Q

What is the difference between autoimmune serology and immunochemistry?

A

Autoimmune serology:
-meaasurement of autoantibodies by various different methods. We can look at the detection of autoantibodies by immunofluorescence. We can also look at autoantibodies by ELISA..
Immunochemistry is measurement of various different serum proteins in serum, eg. CRP (fine nephelometry), cellular plasmin, haptoglobin. Rheumatoid factor is also measured as an antigen, and this can be measured in immunochemistry section.

4
Q

How can we detect ANA?

A

Detection of Antinuclear antibodies by indirect immunofluorescence.
Here we have tissues containing hep2 cells, these are human epithelial cells derived from laryngeal carcinoma cell line. Hep2 cells have a big nucleus. Therefore, anti-nuclear antibodies will bind to these hep2cells that have been treated to expose nuclear antigens. So if patient has ANA, they will bind to these Hep2 cell antigens. We can then detect them. So, you choose your antigen or substrate according to what you want to detect.
So for antinuclear antibodies you use hep2 cells. These are all commercially available.

Enzyme linked immunosorbent assay (ELISA)
Principle is same as ANA.
But Here, label is enzyme linked. You have antigen in plastic well-usually 96 well format.
First 2 rows: known quantities of antigen to get a standard curve.
You add patient serum, if patient has antibodies to the antigen they will bind.
You then add an anti-IgG conjugate. This time it is linked to HRP enzyme, you add substrate for this enzyme, and this will cause a colour change. Colour change is measured and converted from units to ml. It is a goof way to quantitate to quantitate amount of autoantibodies in serum.

5
Q

What are the two types of autoimmune diseases?

A

Autoimmune diseases:
• There is a wide spectrum of autoantibodies one can detect. When we look at autoimmune diseases, there is a wide spectrum of autoimmune diseases. But we can split them into:
-organ specific and systemic autoimmune diseases (non-organ specific).
When we look at organ specific eg: specific organs affected by these diseases.
• Insulin dependent diabetes affecting pancreas.
• Addison’s disease adrenal glands.
Systemic autoimmune diseases: these are widespread. However, in various different systemic diseases, some organs are targeted more than others.
• SLE kidneys, skin.
• In rheumatoid arthritis: joints,
Various different antibodies can be found in these diseases which we can use to aid in the diagnosis.
Autoimmune serology involves the detection of serum antibodies in organ specific and systemic autoimmune diseases.

6
Q

AutoAntibodies to Thyroid stimulating hormone receptor causes what disease

A

Graves disease

7
Q

autoAntibody to acetylcholine receptor

A

Myaasthenia gravis

8
Q

autoantibody to islet cells

A

diabetes mellitus 1

9
Q

autoantibody to intrinsic factor

A

pernicious anaemia

10
Q

autoantibody to endomysial/tTG

A

Coeliac disease

11
Q

ANA

A
  • Antinuclear antibodies
  • directed against a range of target nuclear antigens.
  • They can be detected by various methods, eg. Indirect immunofluorescence and hep 2 cells.
  • Using immunofluorescence and hep2 cells,
  • ANA can give different patterns, these different patterns are important as they are associated with different connective tissue disease, not that specific but allow us to do further tests.
12
Q

ANA

A

• Antinuclear antibodies
• directed against a range of target nuclear antigens.
• They can be detected by various methods, eg. Indirect immunofluorescence and hep 2 cells.
• Using immunofluorescence and hep2 cells,
• ANA can give different patterns, these different patterns are important as they are associated with different connective tissue disease, not that specific but allow us to do further tests.
With immunofluorescence, ANA give different patterns associated with different connective tissue diseases.
ANA test is a highly sensitive test therefore useful test for screening.
ANA are present in SLE, mixed connective tissue disease (MTCD), Sjogren’s syndrome.
Screenig test: has high sensitivity, will pick up everyone with the condition/antibodies. ANA are also present in various other conditions and can also be present transiently in infections. This can cause false positives.
ANA are also present in a percentage of healthy individuals and in the elderly. Therefore, it is good as a screening test, but we still need to do further tests.

Most common detection method for ANA is indirect immunofluorescence. However, when we are doing IIF, and an individual is looking at the slide and making a judgement: it is easy to report strong positive and negative, but you can also get borderline.
-it is also subjective, and quite time consuming, newer automated technologies are used also.

13
Q

What tests are required for SLE?

A

-Rheumatoid factor
-ANA
-immunoglobulins
- serum levels: because in autoimmune diseases, if there is polyclonal b activation, immunoglobulins may be raised.
-complement components: C3, C4.
-ACA: anticardiolipin antibodies; depends who test is coming from.
-Other tests: FBC, ESR, CRP.
ENA

14
Q

c3 & c4 levels in SLE are low. Why?

A

-complement is being used up, being used more than they can be produced.
-classical pathway: immunoglobulin mediated. You can have a either lectin or classical.
-ana is positive in sle, we are looking at classical pathway, it is mediated by antigen antibody complexes because immunoglobulins activated, because this pathway is activated by immunocomplexes, which is raised in sle.
-c3 and c4 are low showing there Is activation of the complement pathway.
IgG is raised, this is part of the autoimmune disease with polyclonal activation of the B cells.

15
Q

Homogenous pattern on Hep-2 cells

A

-produced if ANA is present.
-with immunofluorescence you see different patterns.
This is the homogeneous pattern. Hep 2 cells have a very big nucleus.
-you can see uniform nucleus staining which is homogenous and there is a chromatin region which is very pronounced, this is classical of a homogenous pattern.
If you see a pattern like that it is homogenous, and the chromosomal region shows more pronounced intensity.
This is the homogenous pattern. What is it associated?
-you see different patterns with different conditions.
The homogenous pattern associations are:

SLE, drug induced lupus, rheumatoid arthritis, juvenile
What are the antigens that are being detected?
-nuclear antigens but what specifically?
dsDNA, ssDNA histones and chromatin associated antigens.

16
Q

What aare the 2 tests we can do after ana is positive?

A

There are 2 main tests you can do

  • one is antibodies to DNA
  • or antibodies to ENA.
17
Q

What is the crithidia test

A

-kinetoplast.
-you can see the binding of the antibody to ds dna to the dna from the kinetoplast in the crithridia.
The clinical association for this is sle.
ANA used for high sensitivity, so allows you to get patient. Now you are doing a specific test.
If you did crithidia initially without doing ana, you would miss a lot of patients with the antibody.

18
Q

Speckled pattern IIF result clinical association

A

SLE, SLE overlap syndrome, Sjorgrens syndrome, systemic sclerosis (scleroderma).

19
Q

ENA

A

ENA, are soluble nuclear and cytoplasmic components. ENA is a misnomer. When the name was first used, during the extraction process, they called it nuclear antigens, however it does also contain cytoplasmic components.
Patient is anti-ENA positive.
SSA antibodies, also called, Ro, La. They are named after the patients in which these antibodies were first detected. RNP: antibody to nuclear riboprotein. Sm: smith, JO-1, what we find in polymyocytis.
Rheumetic disease: do different autoantibodies.

20
Q

Which antibody is most specific for SLE?

A

Anti smith (>99% specificity, 70% senssitivity).

21
Q

APTT

A

Intrinsic pathway

22
Q

PT

A

Extrinsic

23
Q

SLE

A

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that predominantly affects women of childbearing age. The exact cause is still unknown, but hormonal and immunological influences as well as genetic predisposition are considered likely etiological factors. The presentation of the disease is variable and may range from mild localized symptoms to life-threatening systemic disease. Typical findings include fever and fatigue, a malar rash (facial butterfly rash), myalgia, and arthritis. SLE may affect any organ, but damage to the kidneys (lupus nephritis) or the nervous system is associated with an especially poor prognosis. The diagnosis of SLE is based on clinical findings and is further supported by antibody tests, particularly for ANA and anti-dsDNA. Management consists of supportive measures, such as avoiding sun exposure, and medication adapted to disease severity. Long-term pharmacotherapy typically involves hydroxychloroquine, which has been shown to reduce flares and decrease mortality. For acute flares, glucocorticoids are given as induction therapy, with dose and treatment duration being adapted to the severity of the flares. In severe cases, additional immunosuppressants (e.g., mycophenolate, azathioprine) may be given.

24
Q

SLE DR DEAC PIMP

A

Epidemiology: Sex: ♀&raquo_space; ♂ (10:1)
Peak incidence: women aged 20–40 years; no particular age of manifestation in men
US prevalence: highest in African-American, Hispanic, and Asian populations

Aetiology:
The exact etiology is unknown, but several predisposing factors have been identified:
Genetic predisposition:
HLA-DR2 and HLA-DR3 are commonly present in individuals with SLE
Genetic deficiency of classical pathway complement proteins (C1q, C2, C4) in approx. 10% [2]
Hormonal factors: studies suggest that hyperestrogenic states (e.g., due to oral contraceptive use, postmenopausal hormonal therapy, endometriosis) are associated with an increased risk of SLE. [3]
Environmental factors: UV light, stimulation of immune cells through infection with bacteria and viruses (in particular EBV, which causes disease flares following infection), medications (e.g., procainamide, hydralazine) [4]

Pathophysiology
Hormonal and environmental factors as well as genetic predisposition (see “Etiology” above) → loss of self-tolerance → production of antibodies against perceived nuclear and cellular antigens → damage to tissue via type III hypersensitivity reaction and, to a lesser extent, type II hypersensitivity reaction
Possible mechanisms for the development of autoantibodies [5]
Deficiency of classical complement proteins (C1q, C4, C2) → failure of macrophages to phagocytose immune complexes and apoptotic cell material (i.e., plasma and nuclear antigens) → dysregulated, intolerant lymphocytes begin targeting normally protected intracellular antigens → autoantibody production (e.g., ANA, anti-ds DNA)
Mechanism of tissue damage
Type III hypersensitivity → antibody-antigen complex formation in microvasculature → complement activation and inflammation → damage to skin, kidneys, joints, small vessels
Type II hypersensitivity → IgG and IgM antibodies directed against antigens on cells (e.g., red blood cells) → cytopenia.

Clinical features:
The severity of SLE varies. While some individuals only experience mild symptoms, others suffer from severe symptoms and rapid disease progression. SLE is typically characterized by phases of remission and relapse. It can affect any organ.
Most common symptoms (see also ACR criteria for SLE diagnosis below)
Skin (> 70% of cases)
Malar rash (butterfly rash) with sparing of the nasolabial folds
Photosensitivity
Discoid rash
Oral ulcers
Alopecia (nonscarring)
Periungual telangiectasia
Joints
Arthritis and arthralgia (> 90% of cases)
Mostly nonerosive polyarthritis (normal x-ray)
Fever (> 50% of cases), fatigue (> 80% of cases), weight loss
Other signs and symptoms
Musculoskeletal: myalgia and lymphadenopathy
Serositis: pleuritis and pericarditis; effusions and chest pain may occur
Kidneys: nephritis with proteinuria (see lupus nephritis)
Heart: involvement of the myocardium, pericardium, valves, and coronary arteries; Libman-Sacks endocarditis (LSE)
Lungs: pneumonitis, interstitial lung disease, pulmonary hypertension
Gastrointestinal: esophagitis, hepatitis, pancreatitis
Vascular: Raynaud phenomenon, vasculitis, thromboembolism (see antiphospholipid syndrome)
Neurologic: e.g., seizures, psychosis, personality changes, aseptic meningitis, polyneuropathy, myasthenia gravis
Hematologic: hemolytic anemia, thrombocytopenia, leukopenia; for other features, see “Diagnosis” below.
Eyes: keratoconjunctivitis sicca.

Investigations
Approach [16]
Suspect SLE in patients with symptoms in more than two of the organ systems listed in the ACR criteria for SLE.
Screening test: ANA titer (SLE is unlikely if the test is negative)
↑ ANA titer → confirm diagnosis with tests that are highly specific for SLE
Anti-dsDNA antibody testing: autoantibody against double-stranded DNA (dsDNA)
Positive in 70% of patients and highly specific
Levels correlate with disease activity
Associated with lupus nephritis
Anti-Sm antibody testing
Autoantibody against Smith antigens (nonhistone nuclear proteins)
Positive in only ∼ 30% of patients, but highly specific for SLE
Tests listed in “Other laboratory tests” below may support the diagnosis.
Anti-nuclear antibody (ANA) testing has the highest sensitivity (95%) but low specificity for SLE. Anti-dsDNA antibody and anti-Smith antibody testing are the most specific for SLE.
Diagnostic criteria (according to the American College of Rheumatology, ACR) [17][1]
Requirements: at least 4 of the 11 criteria must be met (specificity: 95%, sensitivity: 85%)
“SOAP BRAIN MD” is the acronym for the ACR diagnostic criteria for SLE:
S = Serositis
O = Oral ulcers
A = Arthritis
P = Photosensitivity

B = Blood disorders
R = Renal involvement
A = Antinuclear antibodies
I = Immunologic phenomena
N = Neurologic disorder
M = Malar rash
D = Discoid rash

Complete blood count and differential: autoimmune hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia
ESR is frequently elevated, while CRP is often normal.
↓ C3 and C4 complement levels
Urinalysis and urine microscopy: proteinuria and/or casts
Additional antibody tests
Antiphospholipid antibodies may be elevated.
Anti-histone antibodies are elevated in drug-induced lupus erythematosus.
Anti-Ro antibodies are elevated in the majority of cases of neonatal lupus erythematosus.
For a list of additional antibodies that may be elevated in SLE, see section on antinuclear antibodies in antibody diagnosis of autoimmune diseases.

Further diagnostics
Lupus band test (LBT): direct immunofluorescence staining of immunoglobulin and complement component deposits (IgG, IgM, IgA and C3); found along the dermoepidermal junction in affected as well as unaffected skin
Kidney biopsy: if lupus nephritis is suspected (proteinuria, red blood cell casts, or acanthocytes in urinary sediment)
Imaging studies: assessment of organ or joint involvement (e.g., x-ray for joint symptoms, ultrasound to evaluate renal complications).

Treatment:
General management
Avoid exposure to UV light (sunlight)
Smoking cessation
Immunize patients before initiating immunosuppressants
UV phototherapy and UV photochemotherapy (PUVA) are contraindicated!
Mild symptoms, no vital organs affected:
Hydroxychloroquine (or chloroquine)
Induction therapy: low dose, short term oral glucocorticoids.
Severe symptoms, no viral organs affected: medium-dose, oral glucocorticoids.
Immunosuppressive agents (e.g , azathioprine, mycophenolate, cyclophosphamide)
Organ damage: High-dose, IV glucocorticoids.

Complications:
Lupus nephritis (LN)
Description:
Most crucial prognostic factor in SLE
Can be nephritic and/or nephrotic (see also overview of glomerular diseases)
Epidemiology: common (∼ 50% of individuals with SLE)
Pathophysiology: mesangial and/or subendothelial deposition of immune complexes (e.g., anti-dsDNA antibodies, anti-Sm antibodies) → expansion and thickening of mesangium, capillary walls and/or glomerular basement membrane [23]
Classification: classified according to different grades of severity (WHO classes I–VI)
Diagnosis
Urine tests: proteinuria, hematuria, cellular casts (red cells, hemoglobin, granular or tubular)
Kidney biopsy: determination of severity of disease
Classically, immune complex-mediated glomerulonephritis
Diffuse proliferative glomerulonephritis (DPGN): characterized by increased glomerular cellularity in more than 50% of the glomeruli.
Electron microscopy typically shows subendothelial deposits leading to capillary (“wire loop”) thickening.
Most commonly seen in SLE and IgA nephropathy, but also other inflammatory, autoimmune, or infectious diseases
Treatment: Depending on the severity of the disease, prednisone, cytostatic drugs (mycophenolate, cyclophosphamide), and general measures to protect the kidneys (e.g., blood pressure control) may be necessary.

Comorbid conditions
Accelerated atherosclerosis and cardiovascular complications (e.g., myocardial infarction)
Pulmonary hypertension
Pancytopenia
Osteopenia/osteoporosis
Antiphospholipid syndrome
↑ Risk of thrombosis (particularly in individuals with antiphospholipid syndrome) → avoid treatment with estrogens.

Prognosis:
Mortality
10-year survival rate > 90%
Mortality is highest in individuals > 45 years of age (65% of deaths)
Causes of death
In early disease
High disease activity with renal or neurological complications
Infections due to immunosuppressive therapy
In late disease: cardiovascular complications, end-stage renal disease , adverse effects of long-term medication
Cardiovascular disease is the most common cause of death in SLE.

25
Q

SLE and pregnancy

A

Characteristics
Fertility is not affected.
Pregnancy may cause flares in disease activity.
↑ Risk of preterm birth, hypertensive complications (preeclampsia), intrauterine growth restriction, fetal AV block, and miscarriage
Risk assessment [26]
Cardiac, lung, and kidney screening
Maternal antibodies: anti-Ro/SSA and anti-La/SSB
Anticardiolipin antibodies and lupus anticoagulant (see antiphospholipid syndrome)
Management
Pregnancy planning and counseling
Prednisolone , azathioprine; cyclosporin, tacrolimus , and hydroxychloroquine are considered safer drug options during preconception, pregnancy, and breastfeeding.
Some immunosuppressive medications used to treat SLE (e.g. mycophenolate and cyclophosphamide) have severe teratogenic and other adverse fetal effects.
Low-dose aspirin is recommended in all pregnant women from 12 weeks gestation
Neonatal lupus syndrome
Associated with the transfer of maternal antibodies (anti-Ro/SSA and anti-La/SSB)
Symptoms:
Periorbital or diffuse rash (often presents in the first weeks after birth)
Cytopenia
Hepatitis, elevated liver enzymes
First- to third-degree congenital AV block

26
Q

Osteoarthritis

A

Osteoarthritis (OA) is a disabling joint disease characterized by a noninflammatory degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. It mainly affects the weight-bearing and high-use joints, such as the hip, knee, hands, and vertebrae. Despite the widespread view that OA is a condition caused exclusively by degenerative “wear and tear” of the joints, newer research indicates a significant heterogeneity of causation, including pre-existing peculiarities of joint anatomy, genetics, local inflammation, mechanical forces, and biochemical processes that are affected by proinflammatory mediators and proteases. Major risk factors include advanced age, obesity, previous injuries, and asymmetrically stressed joints. In early-stage osteoarthritis, patients may complain of reduced range of motion, joint-stiffness, and pain that is aggravated with heavy use. As the disease advances, nagging pain may also occur during the night or at rest. Diagnosis is predominantly based on clinical and radiological findings. Classic radiographic features of OA do not necessarily correlate with clinical symptoms and appearance. If lifestyle changes (moderate exercise, weight loss) and physical therapy fail to improve symptoms, nonsteroidal anti-inflammatory drugs (NSAIDs) in particular, are used for the management of active osteoarthritis. If medical interventions fail to improve the patient’s quality of life, surgical procedures such as joint replacement may become necessary.

27
Q

osteology dr deac pimp

A

epidemiology: Most common joint disorder in the USA, affecting more than 20 million adults
Incidence: increases with age
Sex: ♀ > ♂, especially in patients older than 50 years
Incidence rates in specific joints: knee > hip > hand

Aetiology:
Modifiable risk factors:
Obesity, excessive joint loading or overuse.
Non-modifiable risk factors:
Age >55 years
Familial history
History of joint injury or trauma
Anatomic factors causing asymmetrical joint stress
Hemophillic hemarthroses and deposition diseases that stiffen cartilage
Gender.

Classification:
Idiopathic OA
No identifiable, underlying cause
Genetic factors of causation have been implicated, but not definitively proven.
Secondary OA 
Hemochromatosis
Wilson disease
Ehlers-Danlos syndrome
Diabetes
Avascular necrosis
Congenital disorders of joints
Alkaptonuria
Joint trauma

Pathophysiology:
Joint damage/stress → cartilage damage → decreased proteoglycans levels → cartilage becomes friable and inelastic and starts to degrade → loss of joint space and bony surface → subchondral bone becomes thickened and sclerotic.

Clinical features
Early clinical findings
Pain on exertion, which is relieved with rest
Pain in both complete flexion and extension
Crepitus on joint movement
Joint stiffness and restricted range of motion
Radiating or referred pain (e.g., coxarthrosis may lead to knee pain)
Late clinical findings
Constant pain (including at night)
Morning joint stiffness usually lasting < 30 minutes
More severely restricted range of motion

Subtypes and variants
Heberden’s nodes: Pain and nodular thickening on the dorsal sides of the distal interphalangeal joints (DIP), ♀ > ♂
Bouchard’s nodes: Pain and nodular thickening on the dorsal sides of the proximal interphalangeal joints (PIP), ♀ > ♂.
Hallux rigidus: Arthrosis of the first metatarsophalangeal joint (between the first metatarsal and the first proximal phalanx), characterized by hypertrophy of the sesamoid bones.
Osteoarthritis of the hip and knee
In contrast to osteoarthritis, rheumatoid arthritis does not affect the DIP joints.

Investigations:
Osteoarthritis is usually diagnosed on the basis of clinical and radiographic evidence of joint degeneration.
Radiological signs of osteoarthritis
Irregular joint space narrowing
Subchondral sclerosis 
Osteophytes (also: bone spurs) 
Subchondral cysts
The patient's history and clinical diagnosis are essential for the assessment and treatment of osteoarthritis! Radiographic signs often do not correlate with the patient's perception and clinical findings!

ddx:
DDx of inflammatory arthritis (put on document as well)
Osteoarthritis
Rheumatoid arthritis
Psoriatic arthritis
Gout
Pseudogout
Other differential diagnoses:
Autoimmune-related arthritis (e.g., sarcoidosis, SLE, rheumatic fever, mixed connective tissue disease, polymyalgia rheumatica)
Arthritis associated with Inflammatory bowel disease
Vasculitides
Hemochromatosis
Viral arthritis (e.g., parvovirus B19, hepatitis viruses)
Lyme arthritis
Reactive arthritis (post-urethritis, post-enteritis)
Fibromyalgia

treatment
General
Weight loss
Regular exercise
Shoe inserts (e.g., buffer insoles) in, e.g., valgus deformity of the knee
Targeted muscle growth, physiotherapy, and medical training therapy
Topical and heat therapy
Pharmacotherapy
Peripheral analgesics
Acetaminophen
NSAIDs: e.g., ibuprofen
In combination with PPIs in patients with gastrointestinal risk (e.g., together with glucocorticoids)
Opioid analgesics: e.g., tramadol
Interventional therapy
In severe courses: intraarticular glucocorticoid injections (not a long-term treatment!)
Surgical therapy: if conservative and interventional measures fail
Endoprosthesis (joint replacement)
In case of failure of endoprosthesis or in select OA subtypes (e.g., Heberden’s OA): arthrodesis (operative ankylosis)
Pharmacotherapy should be used as acute and symptomatic therapy only; long-term NSAID therapy should be avoided due to its many side effects!

Complications
Untreated and/or severe cases can result in permanent damage to the joints with stiffening and deformity.
Complications in the upper limbs: rheumatoid hand deformities (see “Clinical findings” above)
Complications in the lower limbs
Baker cyst due to inflammatory joint effusion
Foot impairment: pes plano‑valgus
Other complications [14]
See “Subtypes and variants” above.
Muscle weakness
Lung disease: pleural and parenchymal lung diseases
Cardiovascular disease: increased risk of pericarditis, coronary artery disease, heart failure, atrial fibrillation, and stroke
Vasculitis involving the kidneys and skin
Amyloid A (AA) amyloidosis
Septic arthritis
Osteopenia, osteoporosis, and bone fractures
Sjögren syndrome (secondary form).

Prognosis 
Factors associated with poor prognosis
Prolonged disease progression without initiation of treatment
Late onset (> 60 years of age)
Sex: ♀
Smoking
Social factors (e.g., low socioeconomic status, low level of education)
Laboratory tests associated with worsened prognosis if abnormally elevated
CRP
ESR
ACPA
RF titer
28
Q

Polymyalgia rheumatica

dr deac pimp

A

Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease that mainly affects patients above the age of 50 years and occurs twice as often in women than in men. Patients typically present with new-onset pain in their shoulders, hips or neck, morning stiffness, and systemic symptoms (e.g., fatigue, malaise, B symptoms, and depressed mood). In addition to clinical presentation, the diagnosis is made based on laboratory studies, which usually show a highly elevated erythrocyte sedimentation rate (ESR), while creatine kinase and autoantibodies are negative. Bursitis and serositis in the joints of the shoulder and pelvic girdle on ultrasound may also help to confirm the diagnosis. The most important step in the management of PMR is to administer a low dose of oral glucocorticoids and taper them slowly until full remission is achieved. Patients with polymyalgia rheumatica should be routinely monitored for symptoms of giant cell arteritis because this type of vasculitis commonly develops during the course of disease.

epidemiology:
Sex: ♀ > ♂ (2–3:1)
Peak incidence: 70–79 years; rarely seen in patients < 50 years
More common among individuals of northern European decent
Most common inflammatory rheumatic disease in the elderly (second most common overall)
Women of advanced age are particularly prone to the disease!

Aetiology
Unknown; possible contributing factors are:
Genetic predisposition (e.g., human leukocyte antigen HLA-DR4)
Association with giant cell arteritis: 10–20% of patients with polymyalgia rheumatica also have GCA

Clinical features 
Systemic symptoms
Constitutional symptoms: fever, weight loss, night sweats
Fatigue and malaise
Depressed mood
Symptoms of anemia
Musculoskeletal symptoms: new onset, symmetric pain
Shoulder and pelvic girdle, neck
Worse at night
Morning stiffness (> 45 min)
Subjective weakness
∼ 10–20% of patients with polymyalgia rheumatica also develop typical symptoms of giant cell arteritis. 

Diagnostics
↑↑ ESR, specifically > 50 mm/h
↑ CRP
Leukocytosis
Normochromic anemia
Normal creatine kinase, negative rheumatoid factors and no autoantibodies
Bursitis on ultrasound of affected joints

DDx:
Giant cell arteritis
Both diseases often coexist and share common findings (e.g., elevated ESR, B symptoms)
May develop during the course of PMR (patients should be routinely evaluated for symptoms of GCA)
Rheumatoid arthritis: positive rheumatoid factor and/or anti-CCP antibodies
Polymyositis and dermatomyositis: ↑↑ serum creatine kinase (normal in PMR)
Fibromyalgia: normal laboratory values
The differential diagnoses listed here are not exhaustive.Giant cell arteritis
Both diseases often coexist and share common findings (e.g., elevated ESR, B symptoms)
May develop during the course of PMR (patients should be routinely evaluated for symptoms of GCA)
Rheumatoid arthritis: positive rheumatoid factor and/or anti-CCP antibodies
Polymyositis and dermatomyositis: ↑↑ serum creatine kinase (normal in PMR)
Fibromyalgia: normal laboratory values
The differential diagnoses listed here are not exhaustive.

Treatment
Low-dose of oral glucocorticoids (alternative: IM glucocorticoids)
If symptoms improve (usually within 2–4 weeks): slowly taper and eventually stop glucocorticoids
No improvement after 2 weeks or relapse: increase dose

29
Q

Giant cell arteritis Dr deac pimp

A

Giant cell arteritis (GCA) is a type of autoimmune vasculitis that causes chronic inflammation of large and medium-sized arteries, in particular the carotid arteries, its major branches, and the aorta. It is most common in white women over the age of 50, and approximately 50% of patients also have polymyalgia rheumatica. Patients usually present with constitutional symptoms (e.g., fever, weight loss, night sweats, fatigue, and malaise), new-onset headache, a tender, hardened temporal artery, jaw claudication, or amaurosis fugax. Laboratory tests typically show signs of inflammation (e.g., elevated erythrocyte sedimentation rate and CRP), and temporal artery biopsy should be performed to confirm the diagnosis. The classic histopathological findings are mononuclear infiltration of the vessel wall and formation of giant cells. If GCA is suspected, prompt administration of glucocorticoids is essential to reduce the risk of permanent vision loss and cerebral ischemia.

Epidemiology
Sex: ♀ > ♂
Peak incidence: 70–79 years; rarely seen in patients < 50 years
Most common among individuals of northern European descent
Women of advanced age are particularly prone to the disease!

Aetiology:
Unknown; possible contributing factors include:
Genetic predisposition (e.g., human leukocyte antigen HLA-DR4)
Viral infections (e.g., parvovirus B19)
Association with polymyalgia rheumatica (PMR): 40–50% of patients with giant cell arteritis also have PMR.

Pathophysiology
Giant cell arteritis is thought to be due to a cell-mediated immune response to endothelial injury. However, the initiating factors are not fully understood.
Inflammation
Activation of dendritic cells in the adventitia of blood vessel walls → Dendritic cells recruit Th1 cells, CD8+ T cells, and monocytes.
Monocytes differentiate to macrophages and giant cells, which produce cytokines (e.g., IL-6, TNF-α) that augment the inflammatory response.
Local vascular damage: macrophages produce metalloproteinases → destruction of vessel wall structures (e.g., internal elastic lamina)
Concentric intimal hyperplasia: macrophages and giant cells produce PDGF and VEGF → stimulate intimal proliferation → reduced blood flow and ischemia

Clinical features:
Constitutional symptoms
Fever, weight loss, night sweats
Symptoms of anemia: fatigue and malaise
Symptoms of arterial inflammation: extracranial branches of the common carotid, internal carotid, and external carotid arteries (the temporal artery is the most commonly affected vessel)
New-onset headache (can be pulse-synchronous, throbbing, dull); typically located over the temples
Hardened and tender temporal artery
Jaw claudication: jaw pain when chewing
Vision loss
Scintillating scotoma
Amaurosis fugax or permanent loss of vision
Diplopia
Symptoms of polymyalgia rheumatica (if both diseases are present)

Diagnostics:
ACR criteria (3 of the 5 criteria are required)
Age at disease onset ≥ 50 years
Headaches
Abnormalities of the temporal artery
Elevated ESR (≥ 50 mm/h; see “Laboratory tests” below)
Histopathological abnormalities in the temporal artery (see “Temporal artery biopsy” below)
Laboratory tests
↑↑ ESR, specifically > 50 mm/h (However, a normal ESR does not rule out giant cell arteritis!)→ can lead to Rouleaux formation of RBCs
↑ CRP
Mild thrombocytosis
Normochromic anemia
No autoantibodies
Temporal artery biopsy (gold standard): mandatory in all patients

pathology:
Panarteritis of the large and medium-sized arteries
Proliferation of the intima (and subsequent stenosis of the artery)
Fragmentation of the internal elastic lamina
Predominantly mononuclear infiltration of the vessel wall with formation of giant cells

ddx:
Polymyalgia rheumatica
Giant cell arteritis and polymyalgia rheumatica (PR) often occur simultaneously and share common features (e.g., elevated ESR, constitutional symptoms).
PR causes shoulder girdle and pelvic stiffness and pain rather than ocular or cerebral findings.
Other vasculitides
Takayasu arteritis
Polyarteritis nodosa
Granulomatosis with polyangiitis
Systemic lupus erythematosus
Rheumatoid arthritis
Other causes of monocular vision loss, e.g.:
Carotid artery disease
Thromboembolism
Retinal vein occlusion

Treatment:
Ischemic organ damage (e.g., impaired vision): high dose of IV glucocorticoids or oral glucocorticoids
Uncomplicated disease: medium dose of oral glucocorticoids
After symptoms have resolved (usually after 2–4 weeks), slowly taper glucocorticoids to the lowest dose that is needed to control symptoms (The mean duration of treatment is 1–2 years).
Low-dose aspirin to prevent ischemic complications
Tocilizumab (antagonizes IL-6 receptor) may be used to reduce the required dose of steroids.
Immediate administration of high-dose glucocorticoids is crucial to prevent permanent vision loss in patients with giant cell arteritis!

complications
Permanent vision loss: ∼ 20–30% if giant cell arteritis is left untreated
Cerebral ischemia (e.g., transient ischemic attack and stroke): < 2% of cases
Aortic aneurysm and/or dissection: ∼ 10–20% of patients

30
Q

Osteoporosis

A

Osteoporosis is a skeletal condition in which the loss of bone mineral density leads to decreased bone strength and an increased susceptibility to fractures. The disease typically affects postmenopausal women and the elderly, as an abrupt decrease in estrogen and age-related processes play a key role in the development of osteoporosis. Further risk factors include inactivity, smoking, and alcohol consumption. Osteoporosis usually remains asymptomatic until the first occurence of fragility fractures (following minor trauma), particularly of the vertebrae. After repeated vertebral fractures, patients may also develop thoracic hyperkyphosis and lose height. Osteoporosis is diagnosed through a bone density test (dual-energy X-ray absorptiometry), while fractures are usually confirmed through conventional x-ray. Management of osteoporosis includes prophylactic measures and medical therapy. The prophylaxis consists mainly of adequate intake of calcium and vitamin D and regular physical activity with strengthening exercises. Both help to maintain or even increase bone mass and improve balance, thereby reducing the risk of falling. Medical therapy is indicated in cases of severely reduced bone density or osteoporotic fractures. The most commonly used drugs are bisphosphonates, which inhibit bone resorption and can significantly decrease the risk of fractures. There are several other possible medical therapies (e.g., teriparatide, raloxifene), which may be indicated in special cases (e.g., severe osteoporosis, breast cancer prophylaxis required) or if patients have contraindications to bisphosphonates.

31
Q

Osteoporosis DR DEAC PIMP

A

D:
Osteoporosis: insufficient bone strength with increased susceptibility to fractures
Osteopenia: decreased bone strength but less severe than osteoporosis

Risk factors
Cigarette smoking
Family history of osteoporosis
Malabsorption, malnutrition (e.g., a vegan diet low in calcium and vitamin D)
Low body weight
Ddx:
Osteomalacia
Hyperparathyroidism
Metastases
Multiple myeloma
Intraosseous hemangioma

Epidemiology:
Sex: ♀ > ♂ (∼ 4:1)
Age of onset: 50–70 years
Demographics: higher incidence in individuals of Asian, Hispanic and northern European ancestry than in black populations

Aetiology
Primary osteoporosis (most common form)
Type I (postmenopausal osteoporosis): postmenopausal women
Estrogen stimulates osteoblasts and inhibits osteoclasts. The decreased estrogen levels following menopause lead to increased bone resorption.
Type II (senile osteoporosis): gradual loss of bone mass as patients age (especially > 70 years)
Secondary osteoporosis
Drug-induced/iatrogenic: especially after systemic long-term therapy with corticosteroids (e.g., in patients with autoimmune disease)
Other: Long-term therapy with anticonvulsants, L-thyroxine, anticoagulants,proton-pump inhibitors, aromatase inhibitors
Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, renal disease
Multiple myeloma
Immobilization
Alcohol abuse

Clinical features:
Mostly asymptomatic
Pathological fractures: spontaneous fracture following mild physical exertion or minor trauma (e.g., lifting something, bending over, or sneezing/coughing)
Localizations: vertebral (most common) > femoral neck > distal radius (Colles) fracture (Colles fracture), fractures of the long bones (e.g., humerus)
Vertebral compression (crush) fractures are commonly asymptomatic, but may cause acute back pain and possible point tenderness without neurological symptoms
Long-term findings after repeated vertebral compression fractures
→ Decreased height (loss of 2–3 cm with each fracture)
→ Thoracic hyperkyphosis → stooped posture with a “dowager’s hump”

Investigations
DXA (dual-energy X-ray absorptiometry)
Calculates bone mineral density (BMD) in g/cm2
Indications
General recommendation for women ≥ 65 years and men ≥ 70 years
In younger individuals if additional risk factors are present (e.g., prolonged glucocorticoid use, low BMI (< 21 kg/m2) or weight < 127 lb, alcohol use, smoker, amenorrhea)
Results: T-score
Osteoporosis: T-score ≤ -2.5 SD
Osteopenia: T-score of -1 to -2.5 SD
Plain radiography
If osteoporosis is diagnosed: radiographic assessment of the whole skeletal system is recommended, particularly if a fracture is already suspected or height loss has occurred
Increased radiolucency is detectable in cortical bones once 30–50% of bone mineral has been lost
Osteoporosis can be diagnosed if vertebral compression fractures are present
Commonly an incidental finding because such fractures are typically asymptomatic
Clinical chemistry: usually normal (see Laboratory evaluation of bone disease), but some markers may be used for assessing risk of fracture
Urine: ↑ cross-links (e.g., deoxypyridinoline), markers of bone turnover
Blood tests
Primary osteoporosis:
Alkaline phosphatase possibly elevated
Other parameters normal (e.g., serum calcium, phosphate)
Secondary osteoporosis: abnormal results depending on underlying disease (e.g., hypercalcemia in hyperparathyroidism)
Pathology:
Thin, disconnected trabecular structures
Attenuated, pitted cortical bone
Increased osteoclast number and activity
Osteoporosis is diagnosed if T-score ≤ -2.5 SD and/or a fragility fracture is present.

Management
Lifestyle measures
Diet
Avoid alcohol and nicotine
Sufficient intake of calcium and vitamin D
Physical activity with strength and balance training
Avoid or minimize glucocorticoids
Medical therapy
Indication
History of fragility fractures
T-scores ≤ -2.5
T-score between -1 and -2.5 with severely increased risk of fracture
Drugs
1st-line treatment: bisphosphonates (alendronate, risedronate); inhibit osteoclasts and therefore bone resorption
Alternative treatment options: in the case of contraindications/unresponsiveness to bisphosphonates or certain risk factors
Teriparatide (parathyroid hormone analog): alternative for severe osteoporosis (T-score ≤ -3.5) or for patients with contraindications to bisphosphonates
Raloxifene (selective estrogen receptor modulator, SERM) for patients with contraindications to bisphosphonates or those who also require breast cancer prophylaxis (but increases the risk of thromboembolism)
Denosumab (monoclonal antibody against RANKL) : for patients with impaired renal function, or no success with bisphosphonates
Consider hormonal therapy
Estrogens: for women with intolerance to 1st- or 2nd-line treatment options or with persistent menopausal symptoms
Usually in combination with progestin
Contraindications: breast cancer, coronary heart disease, deep vein thrombosis
Testosterone: for men with hypogonadism
Bisphosphonates should be taken in the morning and evening at least 30 minutes before meals to prevent bisphosphonates from forming complexes with calcium. To prevent esophagitis, they should also be taken with plenty of water and an upright position should be maintained for at least 30 minutes following intake!

32
Q

Rheumatoid arthritis

A

Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by joint pain, swelling, and synovial destruction. RA predominantly affects middle-aged women. The condition can also cause various extra-articular manifestations such as rheumatoid nodules and pulmonary fibrosis. Diagnosis is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically used for diagnosis. Early intervention with disease-modifying antirheumatic drugs (DMARDs) plays a decisive role in successful treatment. RA is not curable, but early effective treatment may help offset severe complications (e.g., permanent damage to the affected joints).

33
Q

Dr DEAC PIMP Rheumatoid arthritis

A

Epidemiology:
Prevalence: ∼ 1% in Caucasians; lower in African and Chinese population [1]
Sex: ♀ > ♂ (3:1)
Peak incidence: 30–50 years

Aetiology:
Chronic inflammatory autoimmune disorder of unknown etiology
Hypotheses suggest the etiology is multifactorial, with the following factors playing a role:
Genetic disposition: RA appears to be associated with specific HLA types (HLA-DR4, HLA-DR1).
Environmental triggers (e.g., infection, tobacco)
Hormonal factors

Pathophysiology: Initially, non-specific inflammation affects the synovial tissue, which is later amplified by activation of T cells (autoimmune response).
With time, it may lead to inflammatory joint effusion and synovial hypertrophy, as well as progressive destruction and deterioration of cartilage and bone.
Synovial lining hyperplasia
Pannus formation along the synovial tissue → produce proteinases → destroy cartilage extracellular matrix
Patients with positive rheumatoid factor (RF) are more likely to develop extra-articular manifestations of rheumatoid arthritis. [7]

Clinical features 
Polyarthralgia
Symmetrical pain and swelling of affected joints (also at rest). 
Frequently affected joints [10]
Metacarpophalangeal joints (MCPJs)
Proximal interphalangeal joints (PIPJs)
Wrist joints
Knee joints
Usually not involved: DIP joints, first CMC joint, and the axial skeleton (except for the cervical spine, see RA of the cervical spine)
Morning stiffness (often > 60 min) that usually improves with activity [11]
Joint deformities
"Rheumatoid hand"  is characteristic, and can include the following deformities:
Deepening of the interosseous spaces of the dorsum of hand 
Swan neck deformity: PIP hyperextension and DIP flexion  
Boutonniere deformity: PIP flexion and DIP hyperextension.
Hitchhiker thumb deformity (Z deformity of the thumb): hyperextension of the interphalangeal joint with fixed flexion of the MCP joint
Ulnar deviation of the fingers
Hammer toe
Atlanto-axial subluxation
DIP joints are not typically affected in RA!

Extra-articular manifestations
Constitutional symptoms: low-grade fever, myalgia, malaise, fatigue, weight loss, night sweats
Skin: rheumatoid nodules
Non-tender, firm, subcutaneous swellings (2 mm–5 cm)
Commonly occur in areas exposed to higher pressure e.g., extensor side of the forearm, bony prominences
Lungs
Fibrosis, pneumoconiosis (Caplan syndrome)
Rheumatoid pulmonary nodules
Pleuritis, pleural effusions
Eye: keratoconjunctivitis sicca, scleritis, and episcleritis
Endocrine and exocrine glands: secondary Sjögren syndrome
Hematological
Anemia of chronic disease
Neutropenia
Splenomegaly (Felty syndrome)
Other musculoskeletal
Tenosynovitis and bursitis
Carpal tunnel syndrome (entrapment neuropathy)
Typical nocturnal paresthesia of volar hand and fingers I–III
Atrophy of thenar muscles → difficulty making a fist; inability to oppose the thumb
Tarsal tunnel syndrome
Heart: pericarditis and myocarditis; higher risk of myocardial infarction, stroke, and CHF
Vascular: peripheral vasculitis manifesting as livedo reticularis, Raynaud phenomenon, purpura, necrosing fingertips or peripheral neuropathy.

Investigations:
The diagnosis of RA is based on diagnostic criteria that include laboratory testing. Imaging may support the diagnosis, but radiological joint findings are no longer included in the criteria, as they often become evident only in late stages of disease.
Laboratory tests
Non‑specific parameters
↑ Inflammatory markers: CRP, ESR correlate with inflammatory activity.
↑ Ferritin as an acute phase protein
Possibly leukocytosis, thrombocytosis
Anemia of chronic disease
Serology (specific parameters)
ACPA (e.g., anti-CCP )
Specificity > 90%
Rheumatoid factor (RF)
IgM autoantibodies against the Fc region of IgG
Low specificity
Antinuclear antibodies (ANA): elevated in 30% of cases
Synovial fluid analysis
Synovial fluid is collected by joint aspiration.
Findings
Cloudy yellow appearance
Sterile specimen with leukocytosis (WBC: 5,000–50,000/μL)
↑ Neutrophils, granulocytes, and ragocytes
↑ Proteins, ↓ viscosity
Possibly rheumatoid factor.
Imaging
Conventional x-ray
Dorso-palmar x-ray of both hands
Radiological findings
Early: soft tissue swelling, demineralization (juxta‑articular)
Late: joint space narrowing, erosions of cartilage and bone, demineralization (generalized)
Even if radiographic findings are normal, RA is still possible!
MRI: (with or without contrast), especially if cervical spine involvement is suspected or in early stages
Ultrasound: joint effusion, formation of pannus
Further diagnostic measures: contrast-enhanced ultrasound, scintigraphy
Before undergoing general anesthesia, airway and neck assessment is crucial in patients with rheumatoid arthritis. Atlanto-axial subluxation may be present, which increases the risk for spinal cord injury. Preoperative flexion-extension radiographs can help to evaluate the position of the cervical vertebra atlas (C1) with regard to the axis (C2).

Pathology:
Synovial pannus formation and bone invasion: proliferative granulation tissue with mononuclear inflammatory cells
Angiogenesis
Synovial lining hyperplasia with mononuclear cell infiltrate
Perivascular inflammatory infiltrates
Fibrin deposition on synovial surfaces
Characteristic histology of rheumatoid nodules: central fibrinoid necrosis with histiocytes and surrounding epithelioid cells

DDx: of inflammatory arthritis

Treatment:
General measures
For acute episodes of inflammation: cryotherapy
Physical and occupational therapy
Physical activity
Acute anti-inflammatory therapy
Indication: acute attack
Glucocorticoids: given until DMARD’s onset of action or as long-term therapy for highly active RA.
Systemic
Intra-articular injections of PRN
Prevention of osteoporosis: optimization of sufficient calcium and vitamin D intake
NSAIDs and COX-2 inhibitors: symptomatic relief without improving prognosis
PPIs are recommended because combining glucocorticoids with NSAIDs substantially increases the risk of GI ulcers.
Long-term anti-inflammatory therapy with disease-modifying antirheumatic drugs (DMARDs)
Induce immunosuppression, leading to potential remission of RA
Reduce mortality and morbidity by up to 30%
Slow progression of disease
Preserve joint function
Limit complications
Slow onset of action (≥ 6 weeks), so symptomatic treatment with glucocorticoids and NSAIDs is often required
Non-biologic agents
Drug of choice: methotrexate (MTX)
First-line treatment for moderate to severe RA
Benefits: highly effective, relatively well-tolerated, low cost, possibly life-prolonging
Gastrointestinal side effects , rash, hepatotoxicity (abnormal liver chemistry), interstitial pneumonitis and pulmonary fibrosis, bone marrow suppression , nephrotoxicity, increased risk of lymphoproliferative disorders, teratogenicity, alopecia [36]
To minimize side effects, folic acid is recommended 24–48 hours after taking MTX.
Do not give NSAIDs on the same day as MTX, as they can worsen the side effects of MTX by inhibiting its renal excretion .
Alternative drugs:
Leflunomide
Hydroxychloroquine
Sulfasalazine: for use in pregnancy
Biologic therapy
Indication: moderate or severe disease activity remaining after three months of DMARD therapy
Should be combined with non-biologic DMARDs
Tumor necrosis factor (TNF) α inhibitors: e.g., adalimumab, infliximab, etanercept
See contraindications to anti-TNF-α treatment.
Others: rituximab (anti-CD20) and anakinra (interleukin-1 receptor antagonist, particularly for Still disease)
Early administration of DMARDs is crucial for a better outcome!

Complications:
Untreated and/or severe cases can result in permanent damage to the joints with stiffening and deformity.
Complications in the upper limbs: rheumatoid hand deformities (see “Clinical findings” above)
Complications in the lower limbs
Baker cyst due to inflammatory joint effusion
Foot impairment: pes plano‑valgus
Other complications [14]
See “Subtypes and variants” above.
Muscle weakness
Lung disease: pleural and parenchymal lung diseases
Cardiovascular disease: increased risk of pericarditis, coronary artery disease, heart failure, atrial fibrillation, and stroke
Vasculitis involving the kidneys and skin
Amyloid A (AA) amyloidosis
Septic arthritis
Osteopenia, osteoporosis, and bone fractures
Sjögren syndrome (secondary form).

Prognosis
Factors associated with poor prognosis
Prolonged disease progression without initiation of treatment
Late onset (> 60 years of age)
Sex: ♀
Smoking
Social factors (e.g., low socioeconomic status, low level of education)
Laboratory tests associated with worsened prognosis if abnormally elevated
CRP
ESR
ACPA
RF titer
34
Q

Psoriatic arthritis

A

Definition: inflammation of joints (primarily on hands, feet, spine) that may occur with psoriasis
Epidemiology: 5–30% of psoriasis patients affected
Clinical features
Psoriasis and psoriatic arthritis may occur independently or together
There are several types of psoriatic arthritis:
Oligoarthritis (most common, accounting for 70% of cases): typically with involvement of both the distal and proximal interphalangeal joints
Spinal involvement (up to 40% of cases)
Other rheumatological features
Enthesitis
Tenosynovitis
Dactylitis: inflammation and swelling of fingers or toes (“sausage digit”)
Arthritis mutilans: destruction of the IP joints and resorption of the phalanges; causes the soft tissue of the fingers to collapse (“telescoping fingers” or “opera glass hand”)
Diagnosis
There is no specific test for diagnosing psoriatic arthritis
The ClASsification Criteria for Psoriatic ARthritis (CASPAR) is helpful for diagnosing psoriatic arthritis (≥ 3 out of the 5 following points required).
Evidence of psoriasis
Psoriatic nail dystrophy
Negative rheumatoid factor (RF)
Dactylitis
Radiologic signs
Imaging studies: joint destruction, ankylosis
Fingers: pencil-in-cup deformity
Spine: syndesmophytes, and in particular asymmetric paravertebral ossification
Treatment
Mild disease: NSAIDs
Moderate to severe disease: disease-modifying antirheumatic drugs (DMARDs)
Physical therapy
If first-degree relatives of patients with psoriasis have joint problems, psoriatic arthritis should be considered!

If first-degree relatives of patients with psoriasis have joint problems, psoriatic arthritis should be considered!

35
Q

Ankylosing spondylitis Dr deac pimp

A

Ankylosing spondylitis (spondyloarthritis), a type of seronegative spondyloarthropathy, is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell’s sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease. The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumor necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life.

Epidemiology
Sex: ♂ > ♀ (3:1)
Age: 15–40 years
Lifetime prevalence in the US: ∼0.5%

Aetiology
Genetic predisposition: 90–95% of patients are HLA-B27 positive

Clinical features
Articular symptoms
Most common presenting symptoms: back and neck pain
Gradual onset of dull pain that progresses slowly
Morning stiffness that improves with activity
Pain is independent of positioning, also appears at night
Tenderness over the sacroiliac joints
Limited mobility of the spine (especially reduced forward lumbar flexion)
Inflammatory enthesitis (e.g., of the Achilles tendon, iliac crests, tibial tuberosities): painful on palpation
Dactylitis
Arthritis outside the spine (hip, shoulder, knee joint)
Extra-articular manifestations
Most common: acute, unilateral anterior uveitis (∼ 25% of cases)
Fatigue, weakness, fever, weight loss
Restrictive pulmonary disease due to decreased mobility of the spine and thorax
Gastrointestinal symptoms: associated with chronic inflammatory bowel disease (∼ 5–10% of cases, see also: ulcerative colitis or Crohn disease)
Prostatitis
Rare
Cardiac: aortic root inflammation and subsequent aortic valve insufficiency, atrioventricular blocks
Kidney: IgA-nephropathy

Investigations
Diagnostic approach
Physical examination, patient history, and pelvic x-ray: If results are conclusive, no additional testing is required!
If inconclusive → HLA-B27 testing
If still inconclusive → pelvic MRI
Clinical tests
Chest expansion measurement: to monitor disease severity
Method: measure chest circumference in full expiration and inspiration
Pathological difference: < 2 cm
Physiological difference: > 5 cm
Spine mobility tests
Schober test : Mark two points, S1 and another point 10 cm above → patient touches toes (without bending the knees) → distance between the two points increases by ≥ 4 cm → physiological test result; a smaller increase in distance between these two points is pathological
Examination of the hip [3]
Mennell sign: tenderness to percussion and pain on displacement of the sacroiliac joints
FABER test: FABER (Flexion, ABduction, and External Rotation) provokes pain in the ipsilateral hip
The degree of decrease in chest expansion is an important determinant of disease severity.
Schober test
Laboratory findings
↑ CRP and ESR
Auto-antibodies (e.g., rheumatoid factor, antinuclear antibodies) are negative
HLA-B27 positive in 90–95% of cases
However, < 5% of HLA-B27 positive individuals have ankylosing spondylitis.
Imaging
X-ray
Helps confirm a diagnosis and evaluate the severity of disease
Changes are generally more evident in later disease.
The changes usually occur symmetrically.
Pelvis (best initial test): to examine the sacroiliac joints
Signs of sacroiliitis, including ankylosis (fusion of the articular surfaces)
Spine
Loss of lordosis with increasing abnormal straightening of the spine
Sclerosis of the vertebral ligamentous apparatus
Syndesmophytes resulting in a so-called ‘bamboo spine’ in anteroposterior radiograph in the later stages (see the table in “Differential diagnosis” below)
Signs of spondyloarthritis, including ankylosis of intervertebral joints [4]
Thorax: ankylosis of costosternal and costovertebral joints
Mild courses may only exhibit inflammatory changes in the sacroiliac joints on x-ray after a number of years.
MRI
More sensitive than CT scan for detecting sacroiliitis [5]
Best method for early detection.

Ddx:
Mechanical low back pain
Fibromyalgia
Disc prolapse
Vertebral osteomyelitis
Other spondyloarthritides (e.g., reactive arthritis, psoriasis arthritis, arthritis associated with inflammatory bowel disease)
Diffuse idiopathic skeletal hyperostosis (DISH; also called Forestier’s disease or hyperostotic spondylosis)
Definition: degenerative disease of the vertebral column (especially the thoracic and lumbar spine), which is characterized by calcification and ossification of spinal ligaments and entheses
Epidemiology
Not related to HLA-B27 [8]
Mostly affects men
Common in patients with diabetes
Clinical presentation
Limited mobility
Mild or even no pain at all
Diagnosis
X-ray of the spine
Formation of osteophytes (see table below)
No sacroiliitis
Treatment: symptomatic
Osteophytes of the spine Syndesmophytes grow vertically, as opposed to osteophytes, which grow horizontally!
Syndesmophytes:
-Ossification or calcification of the annulus fibrosus or a spinal ligament
-symmetrical, vertical growth, directly from vertebral body to vertebral body.
Full manifestation: bamboo spine
Inflammatory spine disease (ankylosing spondylitis).
Osteophytes:
lipping of vertebral bodies
Horizontal growth
Degenerative spine diseases (e.g diffuse idiopathic skeletal hyperostosis).

Treatment
Physical therapy
Consistent and rigorous physical therapy
Independent exercises
Medical therapy
First choice: NSAIDs (e.g., indomethacin)
Additional options
Tumor necrosis factor-α inhibitors (e.g., etanercept, adalimumab) [12]
In case of peripheral arthritis: DMARDs (especially sulfasalazine)
In severe cases: temporary, intra-articular glucocorticoids
Surgery: in severe cases to improve quality of life
Indications
Severe deformity of the spinal column
Instability of the spine
Neurologic deficits
Procedures
Osteotomy
Joint replacement
Spinal fusion
Physical therapy is the most important treatment modality!

Complications:
Complete fusion of the spine → severely limited mobility
Increased risk of osteoporosis → pathological fractures and possibly spinal cord injury
Restricted chest expansion and spine mobility → breathing difficulties