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Internal Medicine: Clinical Immunology - Rheumatology

Official data in SubjectManager for the following academic year: 2019-2020

Course director

Dr. László István CZIRJÁK (czirjak.laszlo@pte.hu), professor

Department of Rheumatology and Immunology

Subject data

Code of subject: OAK-KIR-T  |  2 credit  |  General Medicine |  Clinical module  |  spring

Prerequisites: OAA-IMM-T completed , OAP-BPR-T completed , OAP-PA2-T completed

Exam course: yes

Number of hours/semester

14 lectures + 14 practices + 0 seminars = total of 28 hours

Course headcount limitations

min. 1

Topic

The goal of the course is to learn the basic knowledge of clinical immunology and rheumatology, to practice the examination of patients with musculoskeletal and joint complaints, to learn the basics of clinical immunological problems.

Lectures

  • 1. General characteristics of systemic autoimmune diseases. - Dr. Czirják László István
  • 2. Systemic lupus erythematosus. - Dr. Czirják László István
  • 3. Systemic sclerosis. - Dr. Czirják László István
  • 4. Sjögren´s syndrome. Inflammatory myopathies. - Dr. Czirják László István
  • 5. Systemic vasculitis. Secondary immunodeficiencies. - Dr. Czirják László István
  • 6. Spondylarthropathies. - Dr. Horváth Gábor
  • 7. Rheumatoid arthritis. Diagnosis. Differential diagnostics of arthritis. - Dr. Czirják László István
  • 8. Rheumatoid arthritis. Treatment and monitoring of patients - Dr. Czirják László István
  • 9. Psoriatic arthritis. Juvenile idiopathic arthritis. - Dr. Horváth Gábor
  • 10. Cervical pain, brachialgia - diagnostics and therapy. Tunnel syndromes. Soft tissue rheumatism. - Szendelbacherné Dr. T. Kovács Katalin
  • 11. Low back pain, differential diagnostics of ischialgia. Algodystrophy. Pain relief in rheumatology. - Dr. Minier Tünde
  • 12. Osteoporosis, osteoarthrosis. Osteonecrosis. Diagnosis and treatment of gout and crystal induced arthropathies. - Dr. Sarlós Gézáné (Dr. Varjú Cecilia)
  • 13. Clinical characteristics of metabolic disorders. - Dr. Minier Tünde
  • 14. Fibromyalgia. Physiotherapy of rheumatic disorders. Rehabilitation in rheumatology. - Dr. Sarlós Gézáné (Dr. Varjú Cecilia)

Practices

  • 1. Learn and practice the examination of patients with musculoskeletal complaints. GALS assessment. General characteristics of systemic autoimmune illnesses.
  • 2. Examination of patients with inflammatory rheumatological conditions (RA, SLE, SSc, SS, myositis). Differentiation between pain in degenerative disorders and inflammatory conditions. Differential diagnosis of arthritis.
  • 3. Examination of patients with inflammatory rheumatological conditions (RA, SLE, SSc, SS, myositis). Joint ultrasound examination, capillaroscopy. Differential diagnosis of Raynaud's syndrome.
  • 4. Examination of patients with inflammatory rheumatological conditions (RA, SLE, SSc, SS, myositis). Differential diagnosis of hand and elbow pain.
  • 5. Examination of patients with inflammatory rheumatological conditions (AS, gout). Differential diagnosis of neck and shoulder pain.
  • 6. Rheumatological examination (osteoporosis, osteoarthritis). Differential diagnosis of back pain and limb muscle weakness.
  • 7. Rheumatological examination (most important steps during examination, differential diagnosis of arthritis). Rehabilitation. Physiotherapy. Exercise. Orthesis.
  • 8. .
  • 9. .
  • 10. .
  • 11. .
  • 12. .
  • 13. .
  • 14. .

Seminars

Reading material

Obligatory literature

Literature developed by the Department

Presentations: on NEPTUN Unified Education System

Notes

Recommended literature

Lynn S. Bickley: Bates´ Guide to Physical Examination and History Taking. (The actual version.)
Harrison´s Principles of Internal Medicine Companion Handbook. Short pocket book. (The actual version.)
Philip Seo (with Alan J. Hakim, Gavin P. R. Cluine, Inam Haq): Oxford American Handbook of Rheumatology, Oxford University Press. (The actual version.)

Conditions for acceptance of the semester

Passing one written exam during the semester. Examination of the musculoskeletal system.

Mid-term exams

There is no possibility.

Making up for missed classes

During the practice of another group.

Exam topics/questions

Exam´s questions A. Differential diagnosis, therapy.
1. When do you suspect a systemic autoimmune disease?
2. Necessary procedures if you suspect a systemic autoimmune disease.
Basic laboratory tests, autoantibody screening tests, specific autoantibody tests.
3. Primary, secondary Raynaud´s syndrome. Differential diagnosis,therapy. Evaluation of efficacy. Basic investigations in Raynaud´s syndrome. Diagnostic value of nail fold capillary- microscopy.
4. Differentiating between degenerative and inflammatory rheumatoid conditions.
5. Evaluation of activity and damage in rheumatologic diseases.
6. Differential diagnosis of polyarthritides.
7. Characteristics, diagnosis and differential diagnosis of oligoarthritis and monoarthritis.
8. Differential diagnosis of cervical and shoulder pain.
9. Differential diagnosis of elbow and hand pain.
10. Differential diagnosis of low back pain. Differentiation between inflammatory and non-inflammatory back pain.
11.Rehabilitation of patients with rheumatological and musculoskeletal diseases. Physiotherapy of rheumatic disorders. Physical exercise. Orthesis.
12 Pain relief in rheumatology.
13 Effects and side effects of non steroidal antiinflammatory drugs.
14 Glucocorticoid treatment. Effects, side effects, prevention of side effects.
15 Biological therapies. TNF antagonist biological therapy. Other biological treatments in inflammatory rheumatological diseases. (rituximab,tocilizumab, abatacept, secukinumab). Biosimilars.
15. Infectious side effects of patients with rheumatological disease during systemic treatment (sulphasalazine, methotrexate, leflunomide,azathioprine, corticosteroids, biologicals, kinase inhibitors).


Exam´s questions B. Main inflammatory rheumatic diseases.
1. Diagnostics of rheumatoid arthritis. New classification criteria in rheumatoid arthritis.
Clinical features of the disease. Laboratory and radiological signs.
2. Basic monitoring and therapeutical principals in RA. Assessment of activity and damage.Basic investigations during monitoring of patients.
Activity indexes: DAS28, SDAI, CDAI. What is HAQ index used for? Therapeutical principals in rheumatoid arthritis. Early treatment. Disease modifying therapy. Treat to target (T2T). Strict monitoring of patients.
3. Treatment of RA. Disease modifying drugs in rheumatoid arthritis. Dosage, side effects,
monitoring of patients during treatment with sulphasalazine,methotrexate, leflunomide.
Dosage, side effects, monitoring of patients during treatment with biological therapy, kinase inhibitors. What are the indications for switching disease modifying therapy in rheumatoid arthritis? Assessment of efficacy in the treatment of RA.
4. Diagnosis of SLE. General characteristics, diagnostic steps. Internal manifestations in
lupus. Laboratory tests in lupus. Lupus nephritis. Central nervous system manifestations in lupus.
5. Management and treatment of SLE. Monitoring lupus patients. Therapeutical principals in lupus. Assessment of disease activity and monitoring damage.
6. Primary, secondary antiphospholipid syndrome. Laboratory diagnostics,symptoms, treatment.
7. Sjögren's syndrome - general characteristics. Principals of diagnosis and treatment.
8. Systemic sclerosis. Clinical features, diagnosis. Therapy,assessment of efficacy during
treatment.
9. Myositis. Main clinical features of polymyositis and dermatomyositis. Classification. Pharmacological and nonpharmacological treatment of myositis. Assessment of efficacy during treatment.
10 Systemic vasculitis. Classification. Primary, secondary vasculitides. Polymyalgia rheumatica, arteritis temporalis. Clinical features and therapy of ANCA associated vasculitides.
11. General characteristics of spondylarthropathies. Peripheral and axial manifestations. Enthesitis. Extraarticular manifestations.
12 Ankylosing spondylitis. Inflammatory back pain. Axial and peripheral involvement in spondylarthropathies. Clinical features and therapy of ankylosing spondylitis. Pharmacological and nonpharmacological treatment of ankylosing spondylitis. Assessment of efficacy during treatment.
13. Psoriatic arthritis. Spondylarthropathies in inflammatory bowel disease.
14. Autoinflammatory syndromes. Sarcoidosis. Macrophage activation syndrome.


Exam´s questions C. Non inflammatory rheumatic diseases.
1. Osteoporosis, clinical features and diagnosis. Primary osteoporosis. Differential diagnosis of secondary osteoporosis.
2. Prevention and treatment of osteoporosis. Pharmacological therapies. Risk factors. Frax index. Prevention. Calcium, vitamin D substitution,role of physiotherapy in the management of osteoporosis.
3. Crystal induced arthropathies. Diagnosis and management of gout.
4. Rheumatological manifestations of metabolic disorders. Acromegaly. Musculo-skeletal abnormalities in diabetes mellitus (DISH syndrome). Musculo-skeletal signs in thyroid disease.
5. Diagnosis, pharmacological and nonpharmacological treatment of fibromyalgia syndrome.
6. Diagnosis and management of osteoarthritis. Clinical features and therapy of knee osteoarthritis. Clinical features and therapy of hip osteoarthritis. Degenerative disorders of the cervical and thoracic spine.
7. Osteonecrosis.
8. Soft tissue disorders.
9. Compression tunnel syndromes.
10 Algodystrophy.
11. Primary immunodeficiency snydrome: characteristics of CVID. Secondary immunodeficiency disorders. Issue of infectious foci.
12. Bacterial infectious arthritis.
13. Management of anaphylactic shock. List of most common causes.


Mandatory requirements for a successful exam:
1. When do you suspect a systemic autoimmune disease?
2. Autoantibody screening tests, most important specific autoantibody tests.
3. In case of unknown inflammation, what conditions can be considered?
4. Differentiation between pain in degenerative disorders
(osteoarthritis) and inflammatory conditions (arthritis.
5. Main causes of monoarthritis.
6. Main causes of polyarthritis.
7. Main causes of Raynaud´s syndrome.
8. Main causes of proximal muscle weakness.
9. Main causes of dryness of the eyes.
10. What diagnostic steps should be made in upper limb complaints?
11. Most common rheumatological reasons of back pain.
12. Most common non - rheumatological reasons of back pain.
13. Lumboischialgia (sciatica), clinical features.
14. Clinical signs of L4 root damage.
15. Clinical signs of L5 root damage.
16. Clinical signs of S1 root damage.
17. Side effects of NSAIDs.
18. Contraindications of NSAID therapy. Necessary precautions.
19. Side effects of glycocorticoids.
20. What kind of supportive treatment is necessary in case of systemic
corticosteroid therapy?
21. What is necessary during emergencies in patients on long term
corticosteroid therapy? (infections, injuries)
22. Side effects of cytostatic therapies.
23. Meaning of DMARD.
24. Contraindications and side effects of biological therapy.
25. What are the necessary steps in sterile leukocyturia?

Main rheumatological illnesses.
26. Most common early clinical signs in SLE.
27. Most common laboratory changes in SLE. What is to be done in SLE?
28. Most common clinical signs in antiphospholipid syndrome.
29. Possible reasons of thrombosis in a young patient.
30. Most common early clinical signs in rheumatoid arthritis.
31. Most common laboratory and radiological changes in RA.
32. Most common early clinical signs in ankylosing spondylitis.
33. Most common early clinical signs in psoriatic arthritis.
34. Clinical signs and management in acut arthritis urica.
35. Clinical signs and management in chronic gout.
36. Infectious arthritis, complaints, clinical features, investigations.

Non inflammatory rheumatological conditions.
1. Clinical signs of knee osteoarthritis
2. Clinical signs of hip osteoarthritis
3. Investigations in osteoporosis
4. Calculation of FRAX index
5. Main reasons of secondary osteoporosis
6. Medications that cause osteoporosis. Prevention.
7. Compression fracture of the spine.
8. Most common signs of gout.
9. What should be excluded in case of carpal tunnel syndrome?
10. Management of anaphylactic shock.

Practical skills during patient examination.
1. GALS examination.
2. Characteristic cutaneous signs in rheumatology. (Infectious
arthritis, gout, livedo, scleroderma, erythema, vasculitis, psoriasis).
3. Physical examination of the hand. (synovitis, arterial pulse, skin
signs, characteristic deformities, carpal tunnel syndrome,
Heberden-Bouhard nodes etc.).
4. Differentiation between inflammatory and degenerative back pain.


Pharmacological knowledge necessary in practical and theoretical exam.

Immunosupressive agents.
1. Glycocorticoids
1.1. systemic
- prednisolon
- prednison
- metilprednisolon
2. Specific lymphocyte signaling pathway inhibitors
2.1. Calcineurin-inhibitors
- cyclosporin
- tacrolimus
3. Cytotoxic agents
- azathioprine
- cyclophosphamid
- methotrexate
- mycophenolate-mofetil
4. Antibodies
4.1. Monoclonal antibodies
TNF-alfa or receptor antagonits
- infliximab
- certolizumab
- adalimumab
- golimumab
- etanercept
IL-1 or receptor antagonists
- anakinra
- canakinumab
IL-6 or receptor antagonists
- tocilizumab, sartilumab
IL-12/IL-23
- ustekinumab
IL-17
- secukinumab
CD20
- rituximab
CD80/86 (B7) (costimulation)
- abatacept
- belatacept
5. Other immunosupressive agents
- leflunomide

Rheumatoid arthritis therapy
1. symptomatical
1.1. NSAID
1.2. glucocorticoids
1.3 physiotherapy
2. DMARD - disease modifying antirheumatic drugs
- methotrexate (+leucovorin)
- cyclophosphamide
- leflunomide
- chloroquin and hydroxychloroquin
- sulfasalazine
- monoclonal antibodies (TNF-alfa, B7, IL-1R, IL-6R, CD20) and kinase
inhibitors
(tofacitinib)

Non steroidal antiinflammatory drugs (NSAID)
1.1. salicilate derivates
- acidum acetilsalicilicum
1.2. Para-aminophenol derivates
- paracetamol (acetaminophen)
1.3. Pirazolon derivates
- phenylbutazon
- oxyphenbutazon
- metamizol-Na (noraminophenazon-Na-mesylat)
1.4. acidum acetylicum derivates
- indometacin
- acemetacin
- diclofenac
- aceclofenac
1.5. Propionic acid derivates
- naproxen
- ibuprofen
- dexibuprofen
- ketoprofen
- dexketoprofen
- flurbiprofen
1.6. Enolic acid derivates
- piroxicam
- meloxicam
- tenoxicam
- lornoxicam
1.7. anthranilic acid derivates
- nifluminsav
- mefenaminsav
- etofenaminsav
1.8. COX-2 specific drugs = coxibs
- parecoxib
- etoricoxib
- valdecoxib

Medications affecting bone metabolism, calcium homeostasis
1. medications affecting the OPG-RANKL-RANK axis
- denosumab (recombinant OPG)
2. Parathormone-analogue
- teriparatid
3. D-vitamins (+Ca)
- colecalciferol
- ergocalciferol
- alfacalcidiol
- calcitriol
4. Calcitonin
- synthetic (salmon) calcitonin (salcatonin)
- synthetic (human) calcitonin (recombinant)
5. Bisphosphonates
- etidronate
- clodronate
- tiludronate
- alendronate
- risedronate
- ibandronate
- pamidronate
- zoledronate
6. others:
- stroncium-ralenate
- tibolon
- raloxifen

Gout treatment
1. acute gout treatment
1.1. Colchicin
1.2. NSAIDs
1.3. glucocorticoids
2. Hyperuricaemia treatment
2.1. Uricostatic agents
- allopurinol
- febuxostate
2.2. Uricolytic agents
- rasburicase
- pegloticase
2.3. Uricosuric agents
- probenecid
- sulfinpyrazon
- benzbromaron

Examiners

  • Dr. Czirják László István
  • Dr. Horváth Gábor
  • Dr. Kiss Bernadett
  • Dr. Kurucz Grácia Katalin
  • Dr. Minier Tünde
  • Dr. Sarlós Gézáné (Dr. Varjú Cecilia)
  • Dr. Tamaskó Mónika
  • Dr. Vélin Valentina
  • Gulyás Katinka
  • Szendelbacherné Dr. T. Kovács Katalin

Instructor / tutor of practices and seminars

  • Dr. Czirják László István
  • Dr. Horváth Gábor
  • Dr. Kiss Bernadett
  • Dr. Kurucz Grácia Katalin
  • Dr. Minier Tünde
  • Dr. Sarlós Gézáné (Dr. Varjú Cecilia)
  • Dr. Tamaskó Mónika
  • Dr. Vélin Valentina
  • Gulyás Katinka
  • Szendelbacherné Dr. T. Kovács Katalin