1. Internal Medicine Notes Prepared by: Ali Jassim Alhashli
Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences
Internal Medicine Notes
Rheumatology
Prepared by: Ali Jassim Alhashli
Based on: Kaplan Step 2 CK Internal Medicine

2. Evaluating a Patient with Arthritis
Polyarticular symmetric involvement of joints is seen with:
Rheumatoid Arthritis (RA): it is an inflammatory arthritis.
SLE.
Parvovirus 19.
Hepatitis B.
Monoarticular arthritis is seen with:
Osteoarthritis (OA): chronic presentation. Systemic symptoms are absent. It is a non-inflammatory arthritis.
Gout: acute presentation.
Septic arthritis: acute presentation.
Trauma: acute presentation.
Hemarthrosis (bleeding into a joint such as that occurring in patients with hemophilia).
Migratory polyarthritis: rheumatic fever.
Search for systemic symptoms which the patient might have:
SLE: descussed in details later.
Sjogren syndrome: keratoconjunctivitis sicca (dry eyes/mouth) + enlargement of parotid gland.
Systemic sclerosis: skin involvement + Raynaud phenomena.
Wegner granulomatosis: upper respiratory (rhinitis, sinusitis) + lower respiratory (hemoptysis) + necrotizing glomerulonephritis.
Is there an evidence of joint inflammation?
Examine for joint swelling, warmth, erythema and limitation of movement.
Check for ESR and C-reactive protein (elevated in case of inflammation).
Ask about morning stiffness of the joint (usually < 1 hour).
Evaluating a Patient with Arthritis

3. Evaluating a Patient with Arthritis
When a patient presents to the hospital with joint swelling → take a full history (covering the points mentioned in the previous slide) → then, aspirate fluid in the joint for analysis of the 3 C’s (Cell count, Crystals and Culture):
Disease
Cell count (WBCs)
Crystals/Culture
Osteoarthritis or trauma (non-inflammatory)
WBCs/mm3
Crystals: negative
Culture: negative
Rheumatoid arthritis and gout (inflammatory)
,000 WBCs/mm3
RA: negative crystals and culture.
Gout: needle-shaped crystals, (-) birefringent; culture: negative
Pseudogout: rhomboid-shaped crystals, (+) birefringent; culture: negative
Septic arthritis
< 50,000 WBCs/mm3
Crystals: negative.
Culture: negative if patient is infected with Gonococcus but positive for Staph, Strept and Gram-negatives

4. Evaluating a Patient with Arthritis
Anitnuclear Antibodies (ANAs):
ANAs are found in patient with autoimmunity (those who produce autoantibodies directed against self-antigens).
ANA patterns:
Homogenous (1): nonspecific.
Speckled (2): found in normal people (nonspecific).
Perihperal (3): SLE.
Nucleolar (4): Systemic Sclerosis (SS).
Centromere (5): CREST.
Specific ANAs:
Anti-ds-DNA and anti-SM: SLE
Anti-histone: drug-induced lupus.
Anti-Ro (SSA) and Anti-La (SSB): Sjogren syndrome.
Anti-centromere: CREST.
Anti-RNP: mixed connective tissue disease.
Scl-70: scleroderma.
Jo-1: dermatomyositis. 1 2 3 4 5

5. Evaluating a Patient with Arthritis
Rheumatoid Factor (RF):
It is an autoantibody directed against the Fc-portion of IgG.
Although it is found in 70% of patients with RA, it is not sensitive or specific (why?) → because it can be false-positive in following conditions:
Increased age.
SLE
Sarcoidosis.
Tuberculosis.
Chronic liver diseases.
Syphilis.
But it can be used for prognosis in patient with RA as increased titers of RF is associated with more aggressive disease.
Antineutrophil Cytoplasmic Antibodies (ANCAs):
They are antibodies directed against certain proteins in the cytoplasm of neutrophils.
cANCA: found in < 90% of patients with Wegner granulomatosis.
p-ANCA: found in patients with Polyarteritis Nodosa (PAN) or Churg-strauss.
Antiphospholipid antibody syndrome (anticardiolipin antibodies):
It is a hypercoagulable condition associated with antibodies directed against phosphlipids or cardiolipins.
Laboratory abnormalities: ↑PTT and false-positive RPR/VDRL (syphilis).
Clinical manifestations:
Females: recurrent abortions. Treated with LMWH heparin during pregnancy.
Males: DVT and pulmonary embolism (which can also occur in female patients).

6. Rheumatoid Arthritis (RA)
Definition: it is a chronic, inflammatory, multisystemic disease, the main target being small synovial joints with symmetric involvement (wrist, MCP and PIP joints but sparing DIP joint).
Epidemiology: age (35-50 years); more among females.
Etiology: unknown.
Pathogenesis:
The predominant cells infiltrating the synovium are T-lymphcytes.
Pro-inflammatory cytokines which mediate most of the pathogenic features of RA are: TNF-a, IL-1 and IL-6.
Diagnosis:
Clinical criteria (you need the presence of 4 criteria):
Morning stiffness (< 1 hour) for 6 weeks.
Swelling of wrist, MCP and PIP joints for 6 weeks.
Symmetric joint swelling for 6 weeks.
Swelling of 3 joints for 6 weeks.
Presence of RF or Anti-Cyclic Citrullinated Peptide (anti-CCP which is more specific than RF).
Elevated ESR or CRP.
Investigations:
RF or anti-CCP.
ESR or CRP.
Anemia.
X-ray: showing erosion of joints.
Synovial fluid analysis: ,000 WBCs/mm3; no crystals; negative culture.

7. Rheumatoid Arthritis (RA)

8. Rheumatoid Arthritis (RA)
Extra-articular manifestations:
Damage to ligaments/tendons:
Radial deviation of the wrist with ulnar deviation of digits.
Boutonniere deformity.
Swan-neck deformity.
Rheumatoid nodule:
It is found in 20-30% of patients at areas of mechanical stress (e.g. olecranon, occiput and Achilles tendon).
Felty syndrome: RA + splenomegaly + neutropenia.
Caplan syndrome: RA + pneumoconiosis.
Treatment:
Initially, you start controlling patients with RA with NSAIDs and it is preferred that you choose a COX-2 inhibitor such as celecoxib (they have less GI and renal side effects but risk of cardiotoxicity).
If NSAIDs do not work, move to Disease-Modifying Anti-Rheumatic Drugs (DMARDs).
The beast initial DMARD is methotrexate. Side effects: liver toxicity.
Other DMARDs: hydroxychloroquine (side effect: retinopathy) and sulfasalazine.
If the patient is resistant to treatment with methotrexate, use a biologic agent (TNF-α inhibitor) but you have to screen for tuberculosis first;
Infliximab: it is a monoclonal antibody binding to TNF-α in joint and circulation. It is given as IV infusion and combining it with methotrexate is very effective.
Adalimumab: monoclonal antibody against TNF-α.
Etanercept: it is a human fusion protein.

9. Rheumatoid Arthritis (RA)
Complications of RA:
RA tends to be more aggressive in the following conditions:
High titers of RF.
Diffuse rheumatoid nodules.
Early bone erosions.
Late age of onset.
If a patient with RA presents complaining of neck pain and upper extremity numbness → consider atlantoaxial sublaxation which occurs due to pannus formation in the synovial joint between atlas (C1) and axis (C2). Initially, request x-ray of cervical spine (with multiple views) and then confirm with CT/MRI of the spine. Refer the patient to an orthopedic surgeon or neurosurgeon if there is a positive radiologic finding.
If a patient with RA presents with a swollen painful calf → consider a ruptured Baker cyst (an extension of inflamed synovium into popliteal fossa).

10. Systemic Lupus Erythematosus (SLE)
Definition: it is a systemic disease in which autoantibodies and immune complexes will cause damage to multiple organs and tissues.
Epidemiology: female:male ratio is 9:1.
Diagnosis:
Clinical criteria (you need 4 to diagnose): MD SOAP BRAIN
M = Malar rash (falres with exposure to UV-B light); D = Discoid lupus (characterized by central atrophy and scarring); S = Serositis (pleuritis/pericarditis); O = Oral ulcer; A = Arthritis (polyarticular and symmetrical); P = Photosensitivity; B = Blood disorders (hemolytic anemia, leukopenia or thrombocytopenia); R = Renal disease; A = ANA; I = Immunologic disorders (ds-DNA and anti-SM); N = Neurologic (seizures and psychosis).
Notice that active lupus is followed-up with:
ds-DNA antibodies.
Complement levels (C3 and C4).
Treatment: cytotoxic drugs (e.g. azathioprine) and corticosteroids.
Prognosis: 10-year survival < 85%. The most common cause of disability in patients with SLE is lupus nephritis.
SLE and pregnancy: pregnant females must be screened for presence of anti-Ro (SSA) antibodies because they have the ability to cross the placenta resulting in neonatal lupus and heart block.
Drug-induced lupus:
Etiology: hydralazine, isoniazid, procainamide and quinidine.
Clinical manifestations: arthritis, fatigue, fever and sometimes pleurisy.
Diagnosis: ANA (anti-histone antibodies).
Treatment: stop the drug and symptoms will resolve within 1-2 weeks (this confirms your diagnosis).
Systemic Lupus Erythematosus (SLE)

11. Systemic Lupus Erythematosus (SLE)

12. Scleroderma (Systemic Sclerosis)
Definition: it is a chronic multisystem disease with skin manifestation and involvement of visceral organs (lungs, GI and kidneys).
Clinical presentation:
Skin becomes thickened and shiny (due to accumulation of connective tissue).
All patient have Raynaud’s phenomenon. It is triggered by cold or emotional distress and occurs due to vasoconstriction. It can be primary (with no underlying disease) or secondary (with an underlying disease such as scleroderma) → to differentiate between the two types → nailfold capillaroscopy test is done → by placing a drop of oil on patient’s nailfold at the base of the finger nail and looking under the microscope → patients with secondary Raynaud’s phenomenon will have enlarged, dilated or absent nailfold capillaries.
Pulmonary: pulmonary fibrosis and restrictive lung disease (most common cause of death in patients with scleroderma).
GI: dysphagia, hypomotility of small intestines with bacterial overgrowth and malabsorption and dilation of large intestine with formation of large diverticula.
Renal: malignant hypertension which can results in acute renal failure. This is treated with ACE inhibitors.
CREST syndrome (limited scleroderma):
C: Calcinosis (formation of calcium deposits in any soft tissue).
R: Raynaud’s phenomenon.
E: Esophageal dysmotility.
S: Sclerodactyli.
T: Telangiectasias.
Diagnosis:
Scleroderma: Scl-70 antibodies.
Limited scleroderma: anticentromere antibodies
Treatment: there is no cure for scleroderma but you can manage symptoms
Skin manifestation: D-penicillamine.
Severe Raynaud’s phenomenon: calcium-channel blockers (e.g. nifedipine).
Malignant hypertension: ACE-inhibitors.
Scleroderma (Systemic Sclerosis)

13. Scleroderma (Systemic Sclerosis)

14. Sjogren Syndrome
Definition: it is a chronic autoimmune disease characterized by lymphacytic infiltration of exocrine glands.
Clinical presentation:
Dry eyes and mouth (keratoconjunctivitis sicca).
Enlargement of parotid glands.
Diagnosis:
Anit-Ro (SSA) and anti-La (SSB).
Biopsy of salivary glands: shows lymphocytic infiltration.
Treatment: symptomatic treatment with artificial tears and saliva (e.g. pilocarpine).

15. Seronegative Arthropathies (Spondyloarthropathies)
Seronegative arthropathies include:
Ankylosing spondylitis.
Reactive arthritis.
Psoriatic arthritis.
Enteropathic arthropathy.
All of the above 4 arthropathies share the following characteristics:
Seronegative (ANA negative and RF negative).
Association with HLA-B27.
Involving lower back and sacroiliac joints.
Presence of extraarticular manifestation.
Ankylosing spondylitis:
Definition: it is a chronic inflammatory disease of unknown etiology mainly affecting axial skeleton.
Epidemiology:
Age: 2nd-3rd decade.
More common among males.
90% of patients are positive for HLA-B27.
Clinical manifestations:
Chronic lower back pain and morning stiffness which lasts for at least 1 hour and improves with exercise.
Extra-articular manifestations: anterior uveitis and aortic insufficiency.
Diagnosis:
X-ray: early in the disease there will be sacroiliitis which will progress to fusion of sacroiliac joint + bamboo spine.
Treatment:
NSAIDs.
Physical therapy and exercise.
TNF-inhibitors (works better for axial disease than RA).
Seronegative Arthropathies (Spondyloarthropathies)

16. Seronegative Arthropathies (Spondyloarthropathies)

17. Seronegative Arthropathies (Spondyloarthropathies)
Reactive arthritis:
Etiology: it occurs as a complication to an infection somewhere in the body. There are 2 types:
Reiter syndrome: it occurs after a non-gonococcal urethritis (e.g. Chlamydia, Ureaplasma). Patients have mucocutaneous manifestations: oral/genital ulcers, conjunctivitis, kertaoderma blenorrhagica and arthritis.
Reactive arthritis after an infectious diarrhea with: Campylobacter, Shigella or Salmonella.
Diagnosis: clinical Diagnosis.
Treatment: same as for ankylosing spondylitis.
Psoriatic arthritis:
It commonly involves DIP joints when associated with psoriatic nail disease (pitting of the nails). This arthritis causes deformity and results in sausage-shaped digits.
Enteropathic arthropathy:
It occurs with IBD (Crohn’s disease and Ulcerative Colitis). There might be association with characteristic skin manifestations: erythema nodosum and pyoderma gangrenosum.

18. Seronegative Arthropathies (Spondyloarthropathies)
Keratoderma blenorrhagica
Psoriatic arthritis

19. Definition: it is a chronic, non-inflammatory disease affecting the joints. It results in destruction of cartilage of the joint with secondary remodeling and hypertrophy of the bone.
Epidemiology:
OA affecting knee joint is the most common cause of chronic disability among elderly population.
Risk factors for OA: advanced age, female sex, genetic factors, major trauma to the joint, repetitive stress to the joint and obesity.
Classification:
Idiopathic (most common).
Secondary to other underlying conditions such as:
Gout.
Diabetes and acromegaly.
Valgus or varus deformity
Clinical presentation:
Most commonly involved joint is the knee joint.
Monoarticular, asymmetric joint involvement.
Joint pain increases with exercise and relieved with rest.
Joint involvement is slow, progressive and irreversible.
Physical examination of the joint: no signs of inflammation but there will be crepitations with the movement of the joint.
Diagnosis: clinical + x-ray findings (osteophytes, narrowing of joint space, hypertrophy of subchondral bone with formation of a cyst).
Treatment:
Start patient on acetaminohpen (to relieve his pain).
If it doesn’t work, move to NSAIDs (e.g. ibuprofen).
If still pain cannot be controlled, try intra-articular injections of hyaluronic acid.
If medical therapy fails and patient’s quality of life is decreased → knee replacement surgery.
Osteoarthritis (OA)

20. Osteoarthritis (OA)

21. Gout and Pseudogout Gout:
Definition: it is a monoarthritis caused by deposition of uric acid crystals in joints (most commonly involved is the metatarsophalangeal joint of the first toe). As the diseases progresses, other joints can be involved and there might be deposition of uric acid crystals in connective tissue (tophi).
Epidemiology: middle-aged males.
Clinical presentation:
Factors precipitating gout: excessive alcohol ingestion, red meat intake, trauma, infection and surgery.
First episode commonly occurs at night (waking patient from sleep). Patient will experience pain in the joint and it will become warm, red and swollen.
Diagnosis:
Synovial fluid analysis (most accurate): ,000 WBCs/mm3; negative birefringent; needle-shaped crystals.
Serum uric acid level: might be elevated (NOT ALWAYS!).
X-ray of a joint involved in multiple gouty attacks: erosive calcifications.
Treatment:
Management of acute attack (aiming to reduce inflammation): NSAIDs, steroids or colchicine.
Chronic management (aiming to reduce uric acid level): allopurinol → if patient cannot tolerate it → febuxostat.
Pseudogout:
Definition: it is a monoarthritis caused by deposition of calcium pyrophosphate crystals in the joint (most commonly involved is the knee joint). Sources of calcium pyrophosphate (remember the 4 H’s): hyperparathyroidism, hemochromatosis, hypophosphatemia and hypomagnesemia.
Epidemiology: elderly population.
Clinical presentation: joint involved becomes red, swollen, warm and painful (similar to gout).
Synovial fluid analysis: ,000 WBCs/mm3; positive birefringent; rhomboid-shaped crystals.
X-ray of a joint might reveal: chondrocalcinosis.
Treatment: manage acute attacks with NSAIDs, steroids or colchicine.
Gout and Pseudogout

22. Gout and Pseudogout

23. Septic Arthritis Etiology:
Young female (age > 40 years) → most common cause of septic arthritis is gonorrhea. This is especially seen during: menses and pregnancy.
Older patients with pre-existing destruction of the joint (e.g. patient has RA) → S.aureus is the most common cause.
Clinical presentation:
Patient might present with fever and monoarthritis with signs of inflammation of the joint involved (warm, red, swollen and painful with decreased range of motion).
Diagnosis:
Synovial fluid analysis: <50,000 WBCs/mm3. Culture and Gram-stain is usually NEGATIVE in gonococcal arthritis (thus you rely on cell count). Culture is positive for septic arthritis caused by other organisms: Staph, Strept, and other Gram-negatives.
Treatment:
Gonococcal arthritis: ceftriaxone.
S. aureus arthritis: nafcillin or vancomycin.

24. Vasculitis Syndromes Wegner granulomatosis:
Definition: it is a small-vessel vasculitis commonly involving respiratory tract and kidneys.
Clinical manifestations:
Respiratory tract:
Upper respiratory tract: chronic rhinitis, sinusitis and rarely nasal ulcers.
Lower respiratory tract: lung nodules causing cough, hemoptysis and dyspnea.
Renal involvement (<80% of patients): most common cause of morbidity and mortality.
Arthritis (<60% of patients).
Diagnosis:
Presence of c-ANCA.
Biopsy (most accurate and confirming) of any involved organ showing: vasculitis + granulomas.
Treatment: all vasculitis are treated with combination of steroids and cyclophosphamide.

25. Vasculitis Syndromes

26. Vasculitis Syndromes Polyarteritis Nodosa (PAN):
Definition: it is a vasculitis of small and medium-sized arteries involving any site of the body EXCEPT THE LUNGS.
Clinical manifestations:
Peripheral neuropathy is common (70%).
Abdominal pain and GI bleeding is also common (might be mistaken for IBD).
PAN might be associated with active haptitis B infection.
Diagnosis:
Presence of p-ANCA (not specific!).
Abdominal angiogram might show: aneurysms and sclerosis.
Biopsy (definitive diagnosis) showing vasculitis.
Treatment: steroids combined with cyclophosphamide.
Churg-Strauss Syndrome:
Definition: it is a vasculitis of small and medium-sized arterities similar in presentation and pathogenesis to PAN but here LUNGS ARE INVOLVED.
Patient has a history of asthma, eosinophilia or other atopic diseases.
Mononeuropathy.
Transient pulmonary infiltrates on CXR.
Sinusitis and allergic rhinitis.
Biopsy (definitive diagnosis).
Treatment: combination of steroids and cyclophosphamide.
Vasculitis Syndromes

27. Vasculitis Syndromes Temporal arteritis (giant cell arteritis)
Definition: it is a vasculitis affecting large-sized arteries supplying the head, eye and optic nerve.
Clinical manifestations:
New-onset headache in patient age < years.
Scalp tenderness (difficulty combing hair).
Decreased/blurry vision or rarely sudden loss of vision.
Jaw claudication (jaw pain when chewing).
Diagnosis:
↑ESR.
Biopsy of temporal artery (definitive diagnosis): demonstrating the giant cells.
Treatment:
Corticosteroids must be started once there is a high-suspicion of your diagnosis (even before taking a biopsy of the temporal artery).

28. Inflammatory Myopathies (Dermatomyositis)
Definition: inflammatory myopathies are inflammatory muscle diseases resulting in progressive muscle weakness.
Clinical manifestations:
Skin manifestations: heliotrope rash around the eyes and sun exposed areas of the body; Gottron’s papules (scaly lesion over knuckles resembling psoriasis).
Proximal muscle weakness (e.g. difficulty getting up from the chair) with positive Gower’s sign.
Ocular muscles are never involved in inflammatory myopathies and this is how you differentiate them from myesthenia gravis and Lambert-Eaton syndrome.
Diagnosis:
↑CPK and aldolase.
Presence of anti-Jo-1 antibodies.
EMG: low-amplitudes and short durations.
Biopsy (definitive diagnosis).
Treatment: steroids.

29. Inflammatory Myopathies (Dermatomyositis)