Rheumatology

SYNOVIAL FLUID ANALYSIS

NONINFLAMMATORY (eg osteoarthritis) INFLAMMATORY (eg RA, crystal-induced, spondyloarthropathies, connective tissue dz, HOA) SEPTIC

FEATURE

Normal

WBCs/m m3

<200

200- 2000

2000 -50.000

>100,000

Polymalgia Rheumatica
Diagnostic Criteria for PMR Age >50. ESR>40mm/h. Neck/bilateral shoulder / pelvic girdle AM stiffness. Symptomatic episodes > 1h in duration. Clinical history >1 month duration. Response to low-dose (15mg/day) steroids.

Remember, PMR patients complain more of stiffness than pain.

Minor criteria include: Weight loss; fever; night sweats,Synovitis. Symmetrical proximal muscle tenderness( no weakness). Alk phos / GGT. Normocytic anemia. Normal CPK, EMG, muscle biopsy. 50% of all PMR patients (TA symptoms) will be found to have giant-cell arteritis on TA biopsy.

fibromyalgia
Diagnosis of exclusion. Female > male . Pain must be present for > 3m. Multiple tender points at least 11points . Pts are poorly able to localize the pain. Nervousness is frequent concomitant. TTT: Aerobic exercise. TCA. ( Tricyclic antidepressant).

DD OF MORNING STIFFNESS/ PAIN WORSE IN AM

Rheumatoid arthritis. Difficulty doing up buttons Ankylosing Spondylitis. LBP + stiffness radiating to buttocks and thighs polymaylgia Rheumatica (PMR) Difficulty getting out of bed Fibromyalgia

Osteoarthritis
Bouchards nodes are proximal interphlangeal nodes. Heberden's nodes are distal interphalangeal nodes. X ray features of osteoarthritis are: joint space narrowing ,osteophytes , subchondral sclerosis & subchondral cysts.

Rheumatoid arthritis

Seven diagnostic criteria for Rheumatoid arthritis

Morning stiffness. Arthritis of 3 joint area. Arthritis of the hand joint. Arthritis symmetric. Rheumatoid nodules. Serum Rheumatoid factor. Radiographic changes. * In order to have RA, you must have 4 of the 7 criteria present for at least 6 weeks.

Symptoms and signs

Predominantly peripheral joints are affected symmetrical joint pain, effusions, soft tissue swelling, early morning stiffness. Progression to joint destruction and deformity.

Nodes and nodules in rheumatic diseases

1. Heberden's nodes DIP osteophytes in 1ryOA. 2. Bouchard's nodes PIP osteophytes in 1ry OA. 3. Rheumatoid nodules. 4. Gouty tophi (elbow, ears, heels, PIPs, DIPs). 5. Xanthomata.

Investigations
Check FBC (normochromic normocytic ), ESR, and/or CRP, platelets &WCC are increased. Rheumatoid factor and anti-CCP antibodies are +ve in the majority 60- 70%. A minority have a +ve ANA titre. X-rays normal, periarticular osteporosis or soft tissue swelling in the early stages; Later---- loss of joint space, erosions, and joint destruction.

RHEUMATOID ARTHRITIS

OSTEOARTHRITIS

ETIOLOGY PATTERN of symptoms Predominant HAND joint involvement LAB XRAY findings

Autoimmune disease Morning stiffness

Degenerative disease Worse after effort or as activity progresses, relived by rest CMC, PIP, DIP

PIP, MCP, wrists (symmetric)

+RF, ESR and C-reactive protein 1. Periarticular osteopenia. 2. Marginal bony erosions. 3.Symmetrical narrowing of the joint space.

Normal RF, ESR, CRP 1. Osteophyte formation 2. Subchondral sclerosis (no periarticular osteopenia) 3. Joint space narrowing.

DD of symmetrical polyarthropathy
Rheumatoid Arthritis. Viral arthropathy. Psoriatic polyarthropathy.

DMARDs (Disease- modifying antirheumatoid drugs):

2 Key Points: Do not wait to start patients on DMARDs until they have failed multiple courses of NSAIDs but, as soon as the diagnosis of RA is confirmed. Methotrexate is the DMARD of choice in patients with severe disease. Start therapy with 7.5mg weekly and raise the dosage at 1intervals until peak efficacy is achieved.

* DMARD Therapy for RA ("GOLD PILE SCAM") DMARD Gold IM and PO Penicillamine Infliximab (Remicade) Potential Toxicities Requiring F/U Myelosouppression, proteinuria Myelosuppression, proteinuria Flu-like sx, auto-Abs; for patients not responding to methotrexate; given IV Thrombocytopenia, hepatotxicity, diarrehea Reactions at site of SQ injection, flu-like sx Myelosuppression Myelosuppression, myeloproliferative disorders, malignancy, hemorrhagic cystistis Monitoring Studies CBC and urine dipstick for protein CBC and urine dipstick for protein None

Leflunomide (Avara) Etanercept (Enbrel) (a TNF blocker) Sulfasalzine Cyclophosphamide

CBC and AST None CBC, AST, creatinine CBC, urinalysis, and urine cytology

Cyclosporine
Azathioprine

Renal insufficiency, anemia, HTN, hirsutism

Myelosuppression, hepatotoxicity, lymphoproliferative disorders Macular damage Myelosuppression, hepatic fibrosis, pulmonary infiltrates or fibrosis cirrhosis,

creatinine, CBC, K+, LFTs

CBC

Antimalarials (Hydroxycholorquine) Methotrexate

Yearly fundus exams CBC, AST, albumin

Minocycline

Photosensitivity, skin discoloration, GI upset, druginduced hepatitis, dizziness

None

Juvenile chronic arthritis

is rheumatoid factor negative. Different classifications are systemic, pauciarticular and polyarticular. Commonest type is Stills disease.( Systemic onset juvenile R.A ). Peaks of disease are about 5 years and 15 years of age. Typical diagnostic criteria include High spiking fevers; arthralgias/ macular rash, hepatomegaly, splenomegaly, lymphadenopathy, serositis (pleuritis, pericarditis), seronegativity (-veRF; -ve ANA); leucocytosis. Thrombocytosis. Very high serum ferritin.

Diagnosis of Felty's Syndrome

Neutropenia caused by hyperslenism and antineutrophil antibodies in a patient with long term rheumatoid arthritis. Triad of Neutropenia; Seropositive RA; Splenomegaly /hyperslenism. Frequent concomitants Serious infections Anemia, thrombocytopenia. Leg ulcers LN, Hepatomegaly Sjogren's synd. Weight loss.

Still's Disease
WBC--inc

Felty's Syndrome
WBC---dec

Fever

No fever necessary

Seronegative RA

Seropositive RA

Splenomegaly

splenomegaly

Systemic lupus erythematosus

9:1.and Asians. Onset 15-40y. Presentation is variable multisystem involvement must be demonstrated to make a diagnosis: Joints (95%)arthritis, arthralgia, myalgia, tenosynovitis Skin (80%)photosensitivity, facial butterfly rash, vasculitis, hair loss, urticaria, discoid lesions Lungs (50%)pleurisy, pneumonitis, effusion, fibrosing alveolitis Kidney (50%)proteinuria, BP, glomerulonephritis, renal failure Heart (40%)-pericarditis, endocarditis CNS (15%)depression, psychosis, infarction, fits, cranial nerve lesions. Blood; anaemia, thrombocytopoenia, splenomegaly

Diagnostic criteria for SLE

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 4 of 11 for 6 weeks; butterfly rash discoid rash. Photosensitivity Oral ulcer Arthritis Serositis Nephrological; lupus nephrotis Neurological Hematologic; lymphopenia, thrombocytopenia. Immunological; anti DNA ANA

Treatment; Skin only chloroquine. JOINT only; NSAIDs. Other extraarticular; steroid & other immunosuppressants.

Drug-induced lupus
Occurs with minocycline, isoniazid, hydralazine, procainamide,BB, chlorpromazine, sulfasalazine, losartan, and anti-convulsants. Remits slowly when drug is stopped but may need steroid treatment to settle. No nephrological, no neurological, DNA ve Anti histone Ab +ve.

TYPES OF ANTINUCLEAR ANTIBODIES

(ANA)
Following detection of a high titer of ANAs (e.g. 1:160), various subtypes are determined. Examples include: Anti-dsDNA (double-stranded DNA) specific for SLE Anti- histones Drug induced lupus Anti-chromatin= anti-nucleosome antibodies. Anti-ENA (Extractable nuclear antigen)=non-DNA = RNP
Anti-Ro (SS-A) Anti-La (SS-B) Anti-Sm (Smith antigen) Anti-U1RNP (nuclear ribonucleoproteins) Anti Scl-70 (topoisomerase I) Anti-Jo

Antinucleolar20% of systemic sclerosis . Anti-centromere Antibodies to nuclear pore proteins as anti-gp- APA.

Anti-ENA (Extractable nuclear antigen)

Ro/SSA Sjgren's syndrome , 40% SLE, ANA -ve SLE, subacute cutaneous LE & neonatal LE. La/SSB 1ry Sjogren. Anti- Smith (Sm) Ab is very specific for SLE, but only in 25 % . Antibodies to U1-RNP 100% of MCTD, 30-40 % of SLE (+ anti- Smith) & small proportion of patients with localized (linear) scleroderma. Antibodies to topoisomerase I (Scl-70), RNA polymerases I and III systemic sclerosis related disorders. Anti-Jo1 PM especially with IPF.

 Chromatin= histones + DNA.

Anti-chromatin= anti-nucleosome antibodies.

DD of sponylitis
1. Sero ve Spondyloarthoropathies. 2. infections. ( TB , Brucella ).

Spondyloarthoropathies
A- HLA-B27 Rheumatic Diseases:

1. 2. 3. 4. 5.

Ankylosing Spoondylitits (<90% are HLA-B27). Reiter's Syndrome or Reactive arthritis (<80%). Enteropthic spondylitis (75%). Psoriatic Spondylitis (50%).

B- Characteristis: 1- Sacroiliac joint involvement. 2- Peripheral arthritis (usually asymmetric and oligarticular). 3- Seronnegativity (absence of RF or other autonatibodies). 4- Association with HLA-B27. 5- Relatively early age of onset (<40). 6- Enthesopathy. 7- Anterior uveitis. 1- Radiographic findings: a) Erosions. b) Syndesmophytes. c) Bamboo spine. D) fusion. 2- Enthesopathic involvement a) Plantar fasciitis. b) Achilles tendonitis. 3- Iritis (an important clue in spondyloarthropathies).

ankylosing spondylitis

Schober's test

Schober's test assesses the amount of lumbar flexion. In this test a mark is made at the level of the posterior iliac spine on the vertebral column, i.e. approximately at the level of L5. The examiner then places one finger 5cm below this mark and another finger at about 10cm above this mark. The patient is then instructed to touch his toes. If the increase in distance between the two fingers on the patients spine is less than 5cm then this is indicative of a limitation of lumbar flexion.

 TTT; 1. Symptoms modifying; NSAIDS 2. Disease modifying; infliximab, methotrexate.

 Reactive arthritis Often asymmetrical aseptic arthritis

Occurs 2-6wk. after bacterial infection elsewhere e.g. gastroenteritis (salmonella, campylobacter), GU infection (chlamydia, gonorrhoea). Management: NSAIDs, physiotherapy, and steroid joint injections. Recovery usually occurs within months. A minority develop chronic arthritis requiring disease-modifying drugs. Reiter's syndrome: Polyarthropathy, urethritis, conjuctivitis. Affects men with HLA B27 genotype. Commonly follows GU or bowel infection. Joint and eye changes are often severe. characteristic mucocutaneous changes oral ulcers , circinate balanitis , keratoderma blenorragicum.

Enteropathic spondylarthropathy
Oligoarticular or polyarticular arthritis linked to inflammatory bowel disease. Includes sacroiliitis, plantar fasciitis, inflammatory spinal pains, and other enthsitides (insertional ligament/tendon inflammation). Arthritis may evolve and relapse/remit independently of bowel disease. NSAIDs may help joint pain but aggravate bowel disease.

circinate balanitis

Psoriatic arthritis
Psoriatic arthritis
Inflammatory arthritis associated with psoriasis. RhF -ve. Presentation variable. Disease modifying drugs (e.g. methotrexate) may improve both skin and musculoskeletal symptoms .
presents as several forms: Symmetrical polyarthritis. Arthritis involving DIP joints. Asymmetrical oligoarthritis including dactylitis (70%) Ankylosing Spondylitis type. Arthritis mutilans.

Among the differentials of ank. Spond. Is DISH. (Diffuse Idiopathic Skeletal Hyperostosis, a form of 1ry osteoarthritis).
a) Patients with DISH are often obese and 60% have diabetes; b) 'stiffness' at the spine' yet relatively well-preserved spinal motion. c) Criteria for DISH'
'Flowing' ossification along the anterolateral aspects of 4 contiguous verterbral bodies with preservation of disk height. Absence of SI joint involvement. Intervertebral disk spaces are preserved.

Marked calcification and ossification of paraspinous ligaments occur in DISH. Ligamentous calcification and ossification in the anterior spinal ligaments give the appearance of "flowing wax" on the anterior vertebral bodies. However, a radioucency may be seen between the newly deposited bone and the vertebtral body, Differentiating DISH from the marginal osteophytes in spondylosis.

Diffuse idiopathic skeletal hyperostosis =DISH

vasculitis
Group of diseases in which tissue ischemia and necrosis occur as a consequence of inflammation of blood vessels, either as a primary event or secondary to a systemic disease .1.Autoimmune dis. 2. Infection
3.Malignancy 4. drugs .

Large vessel vasculitis: chronic granulomatous reaction

affecting the aorta and major branches. Medium vessel vasculitis: necrotizing arteritis affecting visceral arteries renal artery leading to renal infarction . Small vessel vasculitis: capillaries, venules, arterioles (glomeruli)leading to glomerulonephritis
..

Clinical Presentation

Constitutional symptoms. Skin: purpura,ulcers , livedo reticularis , nail bed infarcts ,digital gangrene. Eye :episcleritis ,ulcers and vision loss. Lung: dyspnea, hemoptysis. Cardiac: angina, myocardial infarction , heart failure. GIT: abdominal pain, mesenteric ischemia,malabsorpt. Kidney: hematuria, proteinuria, acute/chronic renal failure CNS: Mononeuritis multiplex, sensorymotor

Names and definitions of vasculitides

Large vessel vasculitis

Giant cell (temporal) arteritis
Granulomatous arteritis of the aorta and its major branches, with a predilection for the extra cranial branches of the carotid artery. Often involves the temporal artery. Usually occurs in patients older than 50 and often is associated with polymyalgia rheumatica. Presentation (classical) of Temporal Arteritis Headache, scalp tenderness; jaw claudication; sudden visual loss.

50% of TA patients have symptoms of PMR.

Flase-negative biopsies may occur 2o to presence of "skip lesions" (if a 2cm biopsy is taken the false-neg rate is >5%; therefore a 3-5cm segment biopsy is recommended).

Takayasu's arteritis
Granulomatous inflammation of the aorta and its major branches. Usually occurs in patients younger than 50. Middle aged women 0f patients presents with initial systemic illness of malaise, fever, night sweats, weight loss, arthralgia, and fatigue then subside with more gradual vascular changes. The other half of patients with Takayasu's arteritis present with only late vascular changes, without an antecedent systemic illness.
It is also known as "Pulseless disease" because pulses on the upper extremities, such as the wrist pulse, may not be able to be felt.

Medium sized vessel vasculitis

Polyarteritis nodosa. (classic polyarteritis nodosa)
Necrotizing inflammation of medium-sized without glomerulonephritis or vasculitis in arterioles, capillaries, or venules.

Kawasaki disease .
Arteritis involving medium sized , and associated with mucocutaneous lymph node syndrome.

Fever of 5 days' duration associated with at least 4 of the following 5 change.

Bilateral nonsuppurative conjunctivitis One or more changes of the mucous membranes of the upper respiratory tract, including pharyngeal injection, dry fissured lips, injected lips, and "strawberry" tongue One or more changes of the extremities, including peripheral erythema, peripheral edema, periungual desquamation.

Polymorphous rash, primarily truncal Cervical lymphadenopathy >1.5 cm in diameter

its most serious effect is on the heart where it can cause severe coronary artery aneurysms in untreated children.

Differential diagnosis, including scarlet fever, toxic shock syndrome, juvenile idiopathic arthritis. There is no specific laboratory test for this condition Blood tests CBC reveal normocytic anemia and eventually thrombocytosis ESR will be elevated CRP will be elevated Other optional tests

Electrocardiogram may show evidence of ventricular

dysfunction or, occasionally, arrhythmia due to myocarditis . TTT: 1.Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease[ 2.Salicylate therapy, particularly aspirin, remains an important part of the treatment

Polyarteritis nodosa Necrotizing vasculitis causing microaneurysms in the medium sized arteries. HBsAg Constitutional symptoms: Fever , abdominal pain,weight loss, arthralgia. Cardiac: coronary arteritis , hypertension , heart failure ,pericarditis. CNS: mononeuritis multiplex, sensorymotor polyneuropathy. seizures, hemiplegia.

GIT: abdominal pain, malabsorption Skin : purpura, urticaria, infarcts, livedoreticularis. Blood: eosinophilia ,anaemia , ESR , CRP. Kidney: hypertension, hematuria, proteinuria, renal failure, intrarenal aneurysms. Testicular pain. ANCA is ve. Diagnosis by nerve biopsy of affected nerve . If affected tissue not accessible ....visceral Angio.

Small vessel vasculitis ANCA Positive:

Wegener's granulomatosis Granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis (Necrotizing glomerulonephritis is common). Churg Strauss syndrome Eosinophil-rich and granulomatous inflammation, necrotizing vasculitis involving the respiratory tract, with asthma and eosinophilia. Microscopic polyangiitis (microscopic polyarteritis) Necrotizing vasculitis, with no immune deposits, affecting small vessels . Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs.

Small vessel vasculitis ANCA Negative:

Henoch Schnlein Purpura. Vasculitis, with IgA-dominant immune deposits. Typically involves skin, gut, and glomeruli, and arthralgia or arthritis. Essential cryoglobulinaemic vasculitis. Vasculitis, with cryoglobulin immune deposits, affecting small vessels, and associated with cryoglobulins in serum. Skin and glomeruli are often involved. Cutaneous leucocytoclastic angiitis . Isolated cutaneous leucocytoclastic angiitis without systemic vasculitis glomerulonephritis.

What is ANCA? Autoantibodies against intracellular neutrophil antigens. C-ANCA cytoplasmic anti PR3. P-ANCA perinuclear anti MPO.

vasculitis with a predilection for renal involovement? Small vessel vasculitis.

Medium vessel vasculitis : PAN How does vasculitis affect the kidney?
Urine analysis shows RBCs ,red cell casts and proteinuria common but usually < 3 gm. Pathology The shared glomerular lesion of the pauci-immune smallvessel vasculitides is a necrotizing glomerulonephritis with crescent formation. Early lesions have segmental fibrinoid necrosis with or without an adjacent small crescent. Severe lesions have global necrosis with large circumferential crescents. Renal arteritis affecting the interlobular arteries.

Wegner granulomatosis
Necrotizing granuloma in the respiratory tract(nasal ulcers, epistaxis , sinus involvement, otitis media, oral ulcers ,proptosis). hemoptysis Rapidly progressive glomerulonephritis. C-ANCA +ve in 70%

Wegener Granulomatosis
Clinical Presentation upper respiratory tract Lung involvement in 80%; transient infiltrates or nodular densities may be seen on (CXR) Histopathology (1) vasculitis of small vessels, (2) granulomatous changes, (3) focal necrosis LM :segmental necrotizing. crescents IF: Pauci-immune GN; crescents; tubulointerstitial granulomas EM: No immune deposits are seen Laboratory Diagnosis cANCA is specific and sensitive 20% to 30% have pANCA

Segmental fibrinoid necrosis with nuclear debris and glomerular basement membrane disruption, typical of early stage of pauci-immune crescentic glomerulonephritis

Well-developed cellular crescent with collapse of small amount of remaining glomerular tuft with segmental fibrinoid necrosis and extracapillary fibrin and necrosis

Churg-Strauss Vasculitis
Small vessel vasculitis . eosinophilic pulmonary infiltrates Allergic rhinitis. Nasal polyposis. Asthma Eosinophilia Necrotizing inflammation Almost no kidney affection glomerulonephritis is usually (but not always) mild. Associated with leukotriene antagonist therapy, P-ANCA Usually in 60%. (MPO) positive. +ve

Microscopic polyangitis Small vessel vasculitis Absence of asthma ,eosinophilia,necrotizing inflammation. P-ANCA is +ve in 50% Kidney : Rapidly progressive glomeruloneph.

Treatment for ANCA-associated disease combination of glucocorticoids (1 mg/kg/d) and IV or oral cyclophosphamide (2 mg/kg/d) for 1 year after remission. methylprednisolone at 7 mg/kg/d IV for 3 days, then oral prednisone at 1 mg/kg/d. plasmapheresis in who RPGN or pulm Hge. Sulfamethoxazole/trimethaprim may diminish relapse rates. Course and Prognosis 90% 1-year mortality if left untreated, 90% remission if treated. Relapse occurs in 25% to 50% of patients followed up for 3 to 5 years

Henoch-Schnlein purpura
systemic vasculitis mostly seen in children. It is a multisystem disorder involving the skin, joints ,gastrointestinal and renal tracts.
Aetiology is unknown, but the syndrome is often preceded by infections such as Group A beta hemolytic streptococcal Pathology is due to intravascular deposition of IgA immune complexes.

Patients often present with a skin(palpable purpuric eruption purpuric rash usually involving the buttocks and lower limbs, arthralgia and severe colicky abdominal pain and tenderness caused by vasculitis-induced thrombosis in the gut. Renal involvement commonly presents as microscopic haematuria and proteinuria Hematuria 50%/asymptomatic hematuria proteinuria 40%, nephrotic
syndrome ,acute and chronic renal failure.

Similar to IgA nephropathy , but crescents, are more frequent

Immunoflorescence :IgA mesangial deposition.

Course.
Overall good renal outcome; complete recovery

Therapy.
Symptomatic for mild cases. For severe nephritis, treatment is steroids+/-cyclophosphamide.

Can complement levels help diagnosing vasculitis?

Exclude infection. Low in SLE ,Cryoglobulinemia . Normal in ANCA +ve vasculitis.

essential mixed cryoglobulinemia

essential mixed cryoglobulinemia was appropriate. complexes in which one component, usually IgM, exhibits antibody activity against IgG (i.e., mixed cryoglobulins). The diagnosis of mixed cryoglobulinemia is typically made from the history, skin purpura, low complement levels, and demonstration of circulating cryoglobulins.

CLINICAL PRESENTATION of Mixed Skin manifestations CGs

Palpable purpura (80% in mixed types) Ischemic necrosis ( 020% in mixed types) Livedoid vasculitis (1% in type I, 14% in type III) Cold-induced urticaria (15% in type I, 10% in type III) Acrocyanosis Nailfold capillary abnormalities

Musculoskeletal manifestations
Arthralgias (5% of type I, 20-58% of mixed) Frank arthritis and progressive joint deformity (distinctly rare)

such as arthralgias and myalgias are common in the mixed CGs, but frank arthritis or myositis are rare to uncommon., especially affecting the metacarpophalangeal, proximal phalangeal, knees, and ankles, Neuropathy Sensorimotor neuropathy affects a high percentage of mixed, but clinically significant neuropathy is uncommon., Visual disturbances

Renal manifestations

Membranoproliferative glomerulonephritis described in all types (more common in type II) Intraluminal cryoglobulin deposition Hypertension Nephrotic-range proteinuria with resultant edema
Dyspnea Cough Pleurisy Pleural effusions Abdominal pain (2-22%) Hemorrhage Hepatomegaly or signs of cirrhosis (ie, palmar erythema, abdominal wall collateral vessels, spider angiomata) Splenomegaly lymphadenopathy

Pulmonary manifestations

Gastrointestinal manifestations

abnormal liver function tests

Cryoglobulinemic Glomerulonephritis can be differentiated from idiopathic MPGN by the following findings . (1) Intracapillary thrombi the presence of large deposits filling the capillary lumen. (2) Massive infiltration of capillary spaces by monocytes and polymorphonuclear cells (the exudative component ). (3) possibly some vasculitis in small and mediumsized renal arteries .)25% to 33%). The combination of vasculitis and glomerular thrombi should suggest cryoglobulinemic nephropathy, but proliferative lupus nephritis with associated vasculitis is also in the differential diagnosis.

 Aggressive therapy in idiopathic mixed cryoglobulinemia reserved for patients with acute severe disease (manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy). plasmapheresis (remove the circulation cryoglobulins) with steroids (1000 mg of intravenous methylprednisolone daily for three days , followed by oral prednisone) and cyclophosphamide. Rituximab is a promising alternative treatment option for severe cryoglobulinemic vasculitis and nephritis.

( Hughes Syndrome),

Anti-Phospholipid Syndrome

 disorder characterized by multiple different antibodies that are associated with both arterial and venous thrombo.

 There are three primary classes of antibodies associated with the antiphospholipid antibody syndrome: 1) anticardiolipin antibodies. 2) the lupus anticoagulant . 3) antibodies directed against beta-2glycoprotein 1.

Sensitivity and Specificity for APS

APL Test ACL LA Sensitivity 80-90% Moderate 74% 91% Specificity Low High 85% 99%

2-GP I
APhL

Harris. Lupus, 1998.

 A patient must meet at least one clinical and one laboratory criterion for a diagnosis of APS

Thrombosis
Venous and arterial circulations Embolic risk high Venous > Arterial Occurs in any system or organ with any part of vascular tree involvement possible(Largesmall) Single or multiple vessel involvement Recurrent events common

 This syndrome, termed "catastrophic antiphospholipid syndrome," is defined by the clinical involvement of at least three different organ systems over a period of days or weeks with histopathological evidence of multiple occlusions of large or small vessels.

Catastrophic anti-phospholipid syndrome (CAPS)

steroids or aggressive immunosuppression is not

used unless recurrent thrombotic or ischemic events despite high intensity warfarin therapy. High dose steroid is reserved for treatment of underlying active lupus and not for lab antiphospholipid AB.

Rituximab
Is a humanized mouse monoclonal antibody against the B cell antigen CD20 that results in the prolonged depletion of B cells. CD20 is relatively selectively expressed on preB and mature B cells, but not plasma cells or T cells, and may selectively treat antibodymediated disorders with less immune suppression than other treatment regimens.

Vasculitis mimickers

Subacute bacterial endocarditis. Left atrial myxoma HIV Paraneoplastic syndrome Cholesterol embolization Cocaine and amphetamine use.

Treatment Combined treatment with steroids and cyclophosphamide induces remission in 75% of ptns at 3months and 90% at 6 months. Pulse steroid therapy 7mg/kg for 3 days(IV methyl prednisone) IV cyclophosphamide therapy 0.5g/m2 monthly reaching 1g/m2 based on the leucocyte count. Role of plasma exchange is controversial ,beneficial in dialysis dependant renal failure patients and those with pulmonary hge .

Crystal induced Arthropathy

A 48-year-old gentleman presented with arthritis of rigt ankle for one day. .. S.uric acid : 7.8

.. Synovial fluid : inflammatory with MSU crystals

.. 24-h urine uric acid : 1200 mg. The most likely cause. 1- hyperparathyroidism 3- MPD 5- thiazide therapy 2- hypothyroidism 4-Lactic acidosis

A 52-year-old lady , diagnosed to have gouty arthritis two years back with synovitis right MTP1., subsided with local steroid injection. .. No further attacks since then ..s.Uric acid ranging from 6.8 8.2 ..s.cr : o.8 , No renal stones .. No tophi.

.. She has to start Allopurinol ** YES ** NO

A 58-year-old gentleman , first attack of gout in R knee persistent in the last 6 days
.. The drug to be least effective at this stage : 1- NSAID 3- Colchicin 5- Oral PDN

4- local steroids

A 52-year-old gentleman upon the first attack of gouty arthritis in L MTP1, started Colchicin for the last 2 weeks. Inflammation subsided
.. S.uric acid now is 13 , supposed to start Allopurinol .. You will combine Colchicin until : 1) 3 months 2) 6 months 3) s.U.A < 6 4)s.U.A < 7 5) 6-months after s.U.A < 6

A 48-year-old lady accidentally discovered to have s.UA of 8 mg% .. 24-h urine uric acid was found 1200 mg .. Best way of management : 1) Start Colchicin 2) Observation with regular monitoring 3) Start Prebencid 4) Start Allopurinol 5) Start Allopurinol & Colchicin

A 54-year-old male , diagnosed as gouty arthritis, first attack. .. S.UA : 8 .. S.creatinin : 1.8 .. C.cr : 35 ml/min
Best way of managemeent : 1) Colchicine 0.5 mg OD 2) Colchicine 0.5 mg BD 3) Avoid Colchicine

A 52-year-old lady, four weeks after first attack of gouty arthritis, lab. Investigations revealed : .. S.UA : 10 .. S.cr : 1.9 .. Ccr : 40ml/min
Best way of management : 1) Start Allopurinol 50mg/d,increase to 100 after 2w 2) ,, ,, 100mg/d ,, 200 ,, 3) ,, ,, 300 mg/d 4) ,, ,, 100mg/d, build up to 300mg 5) No need for Allopurinol.

Hyperuicemia
Gout negatively birefringent crystals Hyperuicemia is either 2ry to overproduction (> 800mg / d) 10% or underexcretion (<600mg / 24hrs) 90% . Causes of underexcretion . HARD to .. HTN. Hypothyroidism. Hyperparathyroidism. Acidosis. Renal insuffeciency. Drugs( thiazides duiretics, Alcohol)

Causes of overproduction
Tissue damage . (Rhabdomy, tumor lysis, hemolytic process, exercise). Proliferative disorders.( mylo& lymphoprolif, psoriasis) Gout is associated with : Hypertriglyceridaemia, diabetes, obesity.

serum hyperuicemia is neither necessary nor sufficient to make the diagnosis of gout. A synovial fluid aspirate is necessary for definitive diagnosis. Always remember, for definitive diagnosis, to send the synovial fluid for crystal analysis, gram stain. Alcohol/diet/diuretics are the most common cause of acute gout in the outpatient population. Gout is very uncommon among premenopausal women.

When to treat asymptomatic hyperuricemia?

** Three specific circumstances warrant at least consideration for institution of hypouricemic drugs : 1) Persistent s.urate >13mg/dl in men and >10 mg/dl in women 2) Excretion of U.uric acid >1100 mg/d is associated with 50% risk of uric acid calculi. 3) Patient about to receive radio or chemotherapy that is likely to result in extensive tumour lysis

 Renal disease is a limitation for both allopurinol & colchicine. With allopurinol, there is a consensus that you need to start with a lower dose and only gradually increase it. Uricosurics are not effective if the serum urate is over about 12 mg/dL, Uricosurics also increase the risk of nephrolithiasis. colchicine works only if you use it fairly early in the attack.

 Benzbromarone Benzbromarone, a uricosuric agent that reduces serum uric acid levels in transplant recipients with hyperuricemia and gout. Benzbromarone is an effective uricosuric, even in patients with creatinine clearances as low as 20 mL/min

1. Treat acute flares with antiinflammatory drugs; NSAIDs, colchicine or steroids. 2. Initiate urate lowering drug (Allopurinol) weeks after any acute flare. 3. Choose effective & safe drug e.g. allop allergy, renal disease. 4. Protect against flare from urate lowering drug by adding anti-inflamatory for 6 months after achieving the target. 5. Continue life style modification 6. Monitor/ 2-4 wks till target uric acid< 6 mg/dl. 7. Then Monitor every 6-12 months.

 Inflammatory arthritis due to deposition of pyrophosphate crystals. Chondrocalcinosis may be seen on X-ray (calcification of articular cartilage). Knee, wrist, and shoulder are most commonly affected. causes are: Haemochromatosis. wilson's disease . Hypothyroidism. hyperparathyroidism. hypomagnesaemia. hypophosphataemia Amyloidosis. Aging.DM Chronic renal failure on dialysis. Acute attacks can be triggered by intercurrent illness and metabolic disturbance. Attacks are less severe than gout and may be difficult to differentiate from other types of arthritis. Presence of joint crystals confirms diagnosis. Pseudogout positively birefringent crystals .

Pseudogout

Pseudogout (calcium pyrophosphate "CPPD")

Can mimic and coexist with gout. similar to gout, surgery, trauma, and alcohol may precipitate. Treatment options are similar to gout, except for allopurinol. Pseudo gout, is Positively birifringent under polarized light microscopy.

A 68-year old man presented with sudden severe pain and swelling in the left knee. Synovial fluid analysis shows abundant calcium pyrophosphate dihydrate (CPPD) crystals. Which of the following tests is NOT appropriate for further assessment of this patient illness? A : Creatinine kinase B : Serum calcium C : Thyroid function test D : Serum ferritin level E : Hb AIc.

Crystal Analysis: Gout Versus Pseudogout Feature Crystal Color under polarized light Shape of crystal Birefringence/ rotation under polarized light direction

Gout
Monosodium urate Yellow Needle Negative (counterclockwise)

Pseudogout
Calcium pyrophosphate Blue Rhomboid Positive (clockwise)

 Pain on adduction more with active movement. Characterized by deposition of hydroxy appetite crystals within rotator cuff muscle near humeral attachment most commonly involve supraspinatus tendon. Severe shoulder pain localized mainly to humorous diffusely around antrolateral shoulder. Palpation or compression around the greater tubercle of the humerus causes tenderness. X ray : linear calcific density in supraspinatus tendon. Ttt: intralesional steroids & physiotherapy.

PseudoPseudogout ( calcific tendinitis)

70 years old lady complaining of gradually progressive bilateral lower limb oedema

Paget disease of bone

Paget disease of bone

Paget disease of bone

What are the manifestations? What are the serious complications? What are the biochemical abnormalities?

What is the treatment?

Paget's disease of bone

Accelerated, disorganized bone remodelling due to abnormal osteoclast activity. Affects up to 1:10 of the elderly but only a minority are symptomatic. Presentation. Skeletal Pain ,deformity & fracture. Deformity bowing of weight-bearing bones, especially tibia, femur, Frontal bossing. High COP failure. Complications Pathological fractures; O Arthropathy of adjacent joints. cranial nerve compression., neurological symptoms e.g. deafness, bone sarcoma (10% of those affected >10y.). Investigation. X-ray Distinctive changes; Alk phos--->very high. normal Ca2+, PO4, PTH, bone scan...diffuse density. Urinary hydroxyproline. Management pain and long-term complications with bisphosphonates (e.g. risedronate 30mg/d. for 2mo.).

Paget disease of bone

Pain,deformities,fractures. Hyperdynamic circulation Marked increase of alkaline Phosphatase Bone scan

Bone scan
Normal:
The radioactive tracer is evenly distributed among the bones. No areas of abnormally high or low accumulation are seen.

Abnormal:

The tracer may accumulate in certain areas of the bone, indicating one or more hot spots. Hot spots may be caused by a fracture that is healing, bone cancer, a bone infection (osteomyelitis), arthritis, or a disease of abnormal bone metabolism (such as Paget's disease).

Bone scintigraphy

Normal bone scan.

Bone metastasis

Bone metastasis Paget disease of bone

Pulmonary osteodystrophy

 Hypertrophic osteoarthropathy (or hypertrophic pulmonary osteoarthropathy when there is mesothelioma or bronchogenic carcinoma associated) X rays show periosteal reaction at the ends of the radius and ulnar bones suggestive of periostitis.

Osteomalacia
Osteomalacia is characterized by a low serum calcium and phosphate with elevated serum alkaline phosphatase. Osteomalacia may be caused by deficiency of vitamin D or phosphate deficiency. Skeletal x-rays
osteomalacia present with the pathognomonic Looser zones are linear areas of low density surrounded by sclerotic borders, better observed in the pubic ramus, upper femoral bone, and ribs.

Treatment is with a daily dose of calciferol (20-25 micrograms).

 Nutritional deficiency Impaired absorption ; Small bowel diseases, such as celiac

disease, gastric bypass, steatorrhea, and pancreatic diseases.

Vitamin D deficiency (osteomalacia)

Hepatic disease
impaired 25-hydroxylation of vitamin D, decreased bile salts with malabsorption of vitamin D, decreased synthesis of vitamin Dbinding protein, or other factors. vitamin D dysfunction.

Anticonvulsants Renal failure

decreased conversion of 25-hydroxyvitamin D to its active form 1,25dihydroxyvitamin D. This results in an increase in PTH.

Inherited conditions
vitamin D dependent rickets (type I) or 1-alpha-hydroxylase deficiency . vitamin D dependent rickets (type II )--- Hereditary vitamin D resistance rickets.

X-linked hypophosphataemic Vit D resistant rickets.

serum phospate is low and urine phosphate is high due to inappropriate renal phosphate wasting. Serum parathyroid levels are usually slightly elevated. Clinically, growth retardation that causes very severe rickets, especially in affected males. Treatment is with oral phosphate and high dose activated Vitamin D.

Bone Disease

Serum calcium

Serum phosphorus

Alkaline phosphatase

osteoporosis osteomalacia
Paget disease

Primary
hyperparathyroidism

Renal osteodystrophy

X-linked hypophosphat aemic Vit D resistant rickets.

Behcet's Syndrome
Immune mediated vasculitis, venulitis. Equal sex affection but more severe in males ,Eastern Mediterranean and Asia . C/P; Painful Genital ulcers. Painful Oral ulcers (98%). Ocular disease ( 80%); more common in HLA B5 men; eg uveitis. iritis, retinal vessel occlusions and optic neuritis can be found. Hypopyon uveitis Skin; E.nodosum ( 80%); (F<M; associated with non-deforming arthritis), pyoderma gang, Thrombophlebitits (30%), Thrombophilia. CNS disease (30%); Aseptic meningitis. Meningoencephalitis, TIA-like episodes, headache, papilledema, Cranial nerve pseudobulbar palsies, Ataxia, dementia. Colitis (30%). Associated with HLA-B5. May lead to perforation. Clinically overlaps with IBD. Arthritis ; intermittent, self-limited, not deforming and localized to the knees and ankles. Spondylits, sacroilitis; When present, linked to HLA-B27. Inv; A positive pathergy test refers to skin injury by needle prick leads to a papule or pustule formation in 48 hours TTT; colchicine, prednizone, NSAIDs, thalidomide.

Behcets

Sjgren syndrome
Sjgren syndrome (SS) is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine glands. C/P; sicca symptoms; xerophthalmia (dry eyes), xerostomia (dry mouth), dyspareunia fatigue and parotid gland enlargement. extraglandular features ; arthralgia, arthritis, Raynaud phenomenon, myalgia, pancreatitis, leukopenia, anemia,LN, neuropathy, vasculitis, RTA, and later lymphoma (suspected if low C4, cryo, persistent parotid enlarg, purpura & leukopenia). Primary Sjgren syndrome occurs in the absence of another underlying rheumatic disorder, whereas secondary Sjgren syndrome is associated with another underlying rheumatic disease, such as SLE, RA, or scleroderma.

Inv; ANA 90%, Anti RO & Anti La in 1ry SJ, ESR, CRP, RF, hypergammaglobulinema in 80%. Schirmer's test Management artificial tears , cool drinks, artificial saliva sprays or sugar-free gum. pilocarpine NSAIDs, hydroxycholoquine for arthritis.

Dermatomyositis
C/P; proximal muscle weakness, tenderness. Skin; Raynaulds, Gottron's papules , heliotrope rash around the eye, calcinosis, periungual telangiectasia, mechanics hand, v shaped, shawl sign. Others; Dysphagia. cardiomyopathy, IPF. The condition is associated with carcinoma of the breast, lung, ovary and bowel in old age only. Inv : elevation of muscle enzymes; CPK, LDH, AST. EMG; myopathic pattern (high frequency, low amplitude). ESR, CRP in 5 % only. Autoantibodies; - ANA - anti-jo-1)IPF, mechanics hand, Raynaulds) - anti M2 (classic) - anti SRP (severe rapidly progressive) severe form with cardiac affection. muscle biopsy; inflammatory changes .

TTT; steroids rapid CPK but power takes weeks+/- methotrexate, cyclophosphamide.

Scleroderma

Inv; ANA in 90%, RF in 30% Anti-topoisomerase (= anti Scl 70, specific, in 30%) in diffuse scleroderma. Anticentromere in 50-90% of limited & 10% of diffuse sclero. Anti-RNA polymerase III in renal crises. Patterns; 1. Limited systemic; CREST S (calcinosis, raynaulds, esophageal dysmotility, scleroderma, telangiectasia), tight skin limited to face, neck, distal extremities. cause of death; pulmonary HTN. 2. Diffuse systemic; cause of death; renal crises, worse prognosis. 3. Localized to the skin; morphea (plaques), coup de sabre (linear).

TTT; NSAIDs, PPI, antibiotics for bact overgrowth, VD, PG, Dpenicillamine, ACEI for renal crises.

Overlap Syndromes
E.g. mixed CT disease; SLE, Sclero, PM. +ve anti RNP.

Osteoporosis
**A disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture .
**Bone mineral density (BMD) T-score < 2.5

What are the major risk factors for osteoporosis? Non-modifiable 1) 2) 3) 4) 5) 6) Age. Race ( Caucasian,Asian). Gender (female). Early menopause(<45) Slender built. Positive family history. Modifiable 1) low ca. intake 2) low vit-D intake 3) estrogen deficiency 4) sedentary life 5) smoking 6) alcohol(>2drinks/d) 7) caffeine(>2serving/d 8) medications: (steroids-thyroxine)

Other conditions with low bone mass ** hyperparathyroidism ** Celiac d. ** hyperthyroidism ** Liver d. ** hypogonadism ** I.B.D ** cushing s. ** myeloma ** osteomalacia ** Renal failure ** Drugs : .. Steroids thyroxine cyc,A - heparin

How to interpret BMD

1)T-score : comparison of patients bone mass to that of young normal subject(age 30) 2)Z-score : comparison of patients bone mass to that of age-matched subject

**

indications for BMD:

1)Women aged 65 years and older . 2)Postmenopausal women< 65 years with risk factors for osteoporosis 3)Men aged 70 years and older . 4)Adults with fragility fracture . 5)Adults with a disease or associated with low bone mass or bone loss. 6)Adults taking medication associated with bone loss. 7)Anyone being considered for pharmacological osteoporosis therapy .

Pharmacologic therapy of osteoporosis

1. 2. Ca, vit D Drugs that decrease bone resorption; HRT (Euterine cancer& breast cancer). SERM (selective Estrogen receptor modulators)= agonist on bone & antagonist on breast osteoporosis, br cancer & IsHD. Side effects; flushes, DVT. - Raloxifen (Evista)used in postmenopausal osteoporosis. 3. STEAR= selective tissue estrogenic activity regulator e.g. Tibolon (Levial ) 4. Bisphosphonate (oral alendronate) 5. Calcitonin ; anabolic bone effect, Side effects; nasal congestion, rash. Drugs that increase bone formation; 1. Synthetic PTH (Teripatide). 2. Strontium ranelate (Protelos) dual mechanism , incr bone formation & decrease bone resorption. 3. Others; GH, GHRH, IGF1, anabolic steroids, statins.

Ca, vit D; - ca alone; small effect on BMD, no antifracture effect. - Vit D alone; unknown effect in pt without vit D def. - Ca + Vit D; may BMD, fracture. Raloxifen (Evista ) 60 mg once daily - TTT & prevention postmenopausal osteoporosis. - adv; vertebral fracture,but not non vert fracture, br cancer & IsHD. - Side effects; increase risk of DVT. not effective against non vert fracture. Calcitonin; nasal spray, SC; vertebral fracture ( weak evidence) , small BMD.

HRT
Thromboembolism, breast cancer, TG, risk of fracture, cancer colon, HDL coronary. Contraindications; - Absolute; E dependant tumours; breast, endometrium. Thromboembolic disorder. Abn vaginal bleeding. - Relative; FH of br cancer, GB disease. Endometriosis

 Alendronate (oral daily 10 mg or weekly 70 mg) - mech; taken up by osteoclast apoptosis. - adv; effective against all fractures, long term benefit (10 yrs). - disadv; poor upper GIT tolerance. - contraindications; hypocalcemia, osteomalacia, renal failure, bed ridden, serious oesophageal dis. - side effects; hypocalcemia, PTH, skin rash oral; esophagitis, ulceration. IV; flu like, arthralgia, myalgia, fever, leukopenia, eye inflammation etidronate; phosphate, osteomalacia.

Teriparatide; rh PTH - daily SC, 1st anabolic, all fractures, marked & rapid BMD. - disadv; daily SC, use restricted to high risk pts, osteosarcoma in toxicologic studies. - contraindication; bone dis; paget dis, Hx of bone metastasis or cancer, growing child, bone, hypercalcemia, pregnant, lactation.

The following subjects are candidates for BMD except : 1) A lady of 68 years 2) An obese lady at age of 52(menopause) 3) A man of 74 years age 4) A lady 34-year age with 1ry hyperparathyroidism

A 54-year-old lady advised to do BMD for persistent spine pain, Which revealed : ** T-score
.. L.spine : -2.6 .. F.neck : -1.7 ** All are possible except : 1)Osteoporosis
2)Hyperparathyroidism 3)I.B.D 4)Hypothyroidism 5)Cushing d.

A 52-year-old lady, menopause for 3 years on longterm steroids for her uncontrolled chronic asthma
** BMD done for her revealed : T-score L.spine : -2.0 F.neck : -1.2 ** suggested treatment :
1)Calcium + vitamin-D 2)Calcium + vitamin-D + Alendronate 3)Calcium + vitamin-D + Alendronate + Calcitonin 4) No TTT

A 62-year-old lady presented with severe back pain , she lost about 2 inches of her height. Plain XR revealed farcture of T12 and wedged L3. She is immobile for severe knee OA and on steroids for ILD ** BMD advised revealing : T-score L.spine : -4.2 F.neck : -2.8 ** Best TTT is : 1) Ca + vit-D + Alendronate 2) Ca + vit-D + Calcitonin 3) Ca + vit-D + Teriparatide (PTH) 4) Ca + vit-D + Alendronate + Calcitonin

A 58-year-old lady admitted for fracture neck-femur ** BMD revealed : T-score L.spine : -1.6 F.neck : -2.8
** The drug being least effective is : 1)Alendronate 2) HRT 3) PTH 4) Raloxifene ( SERM)

Gonoccocal arthritis
is a common cause of septic arthritis in which the organism cannot be cultured on routine culture media. Occur in disseminated gonococcal infection. C/P; sexually active individuals, ; (4:1), during menstruation and pregnancy. fever, chills, skin rashes( pustular) , polyarthralgias, and tenosynovitis persistent monoarthritis or oligoarthritis, Inv; The mean synovial fluid WBCs = 50,000 cells/mm3. Cultures of synovial fluid tend to be positive in < 50 % of cases of gonococcal arthritis The joint aspirate should be cultured for N. gonorrhoeae when the history is suggestive. ( chocolate agar or Thayer-Martin medium) cultures from clinically appropriate sites (eg, the pharynx, urethra, cervix, rectum, and skin lesions). Blood cultures are often positive in patients presenting with tenosynovitis and skin lesions alone, PCR screening test for HIV and a syphilis. TTT; , the initial therapy of choice is ceftriaxone (1 gm either IV or IM) or another 3rd G cephalosporin. Fluoroquinolones .

Relapsing polychondritis Associated with autoimmune disease in 30%. Leads to fever, arthralgias, episcleritis, swollen floppy ears. Nasal Septum collapse (the other 'saddle nose' deformity, i.e. not just Wegener's). laryngeal disease hoarseness; respiratory obstruction. Tracheobroncial degeneration recurrent infections, AI/MVP/ Aneurysm in 10%.

Causes of avascular necrosis

SLE . vasculitis & any hypercoagulable state. long term steroids . sickle cell disease. Hip involvement. MRI is the best diagnostic tool.

Causes of Charcots joints:

diabetic neuropathy, syphillis syringomyelia leprosy Behcet's disease Reiter's syndrome ankylosing spondylitis sardoidosis

Causes of Iritis:

 Eosinophilic fasciitis is a disorder characterized by peripheral eosinophilia and fasciitis. Swelling and progressive induration of the skin associated with aching of the extremities and occasional morning stiffness develop over a period of weeks. The distribution most often is in the upper extremity, proximal and distal to the elbow, and in the lower extremity, proximal and distal to the knee. Onset may be acute following some sort of strenuous exercise, or it may be subacute. The diagnosis is confirmed by deep biopsy from skin to muscle.

Eosinophilic fascitis

Eosinophilic fascitis

Rheumatologic Manifestations of sickle cell disease

Gout. Sickle lower extremity arthralgias (knees and ankles most common), myalgias, synovitis. 2ry hemochromatotic (Fe overload 2o to frequent transfusions). Septic arthritis (or osteomyelitis), esp due to Salmonella, particularly if hyposplenic. Aseptic (avascular) necrosis.

Familial Mediterranean fever

AD is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints, fevers and rash. The first episode usually occurs by the age of 20 years, but in some cases, later in life. FMF primarily affects populations originating from the Mediterranean region. A buildup of amyloid. AA amyloidosis commonly involves the kidneys, spleen and GI tract. Colchicine given prophylactically in FMF offers some protection against the development of amyloidosis in most patients.

De Quervain's tenosynovitis is inflammation of the abductor pollicis longus and extensor pollicis brevis. Finkelstein's test is positive. This is performed with the thumb flexed across the palm of the hand, asking the patient to move the wrist into flexion and ulnar deviation. This stresses the tendons of abductor pollicis longus and extensor pollicis brevis and reproduces the pain of de Quervain's tenosynovitis.

 A 15-year-old boy presented with arthralgia, skin rash and haematuria. Renal biopsy showed focal necrotising glomerulonephritis with diffuse mesangial IgA deposits. What is the most likely diagnosis? A : Systemic lupus erythematosus (SLE) B : HenochScholein purpura C : Juvenile rheumatoid arthritis D : Post-streptococcal glomerulonephritis E : Goodpasture's syndrome

 24. A 64-year-old man presents to A&E with a 2day history of increasing pain and swelling of his left knee. He denies a history of trauma. On examination, the knee is hot, red, swollen and extremely tender. Which of the following investigations is most important? A : Plain radiograph of the knee B : Blood cultures C : C-reactive protein (CRP) D : Joint aspiration E : Plasma uric acid level.

64-year-old man with congestive heart failure presents to the emergency room complaining of acute onset of severe pain in his right foot. The pain began during the nightand awoke him from a deep sleep. He reports the pain to be so severe that he could not wear a shoe or sock to the hospital.His current medications are furosemide, 40 mg twicedaily, carvedilol, 6.25 mg twice daily, candesartan, 8 mg once daily, and aspirin, 325 mg once daily. On examination, he is febrile to 38.5C. The first toe of the right foot is erythematous and exquisitely tender to touch. There is significant swelling and effusion of the first metatarsophalangeal joint on the right. No other joints are affected. Which of the following findings would be expected on arthrocentesis? A. Glucose level of <25 mg/dL B. Positive Gram stain C. Presence of strongly negatively birefringent needleshaped crystals under polarized light microscopy D. Presence of weakly positively birefringent rhomboidal crystals under polarized light microscopy E. White blood cell (WBC) count >100,000/L

A 36-year-old woman presents with deteriorating nocturnal paraesthesia affecting both hands. It improves during the morning. Which of the following tests is least likely to be helpful in establishing the cause? A : Thyroid function test B : Rheumatoid factor C : Tinels test D : MRI scan hands E : Urinary hCG.

A 25-year-old woman with a history of 3-second trimester fetal losses is planning a fourth pregnancy. She has evidence of the primary anti-phospholipid syndrome (strongly positive cardiolipin antibody, positive lupus anticoagulant but no evidence of lupus). Which of the following treatment regimens offer her the best chance of having a successful pregnancy? A : Steroids alone B : Steroids combined with low-dose aspirin C : Low-dose aspirin alone D : Low-dose aspirin combined with low molecular weight heparin E : Intravenous immunoglobulin.

Serum biochemistry of a 60 year old man revealed calcium of 1.98 mmol/l and phosphate of 0.55 mmol/l with an alkaline phosphatase of 450 IU/l. Which among the following most suits with the above serum biochemistry? 1) Osteoporosis 2) Osteomalacia 3) Pagets Disease 4) Secondary Hyperparathyroidism 5) Renal failure

A 36-year old woman is referred with a 1-year history of muscle pain, tiredness and sleep disturbance. She denies fever, weight loss and arthralgia. Examination reveals tenderness over her occiput, trapezius and lumbar area. Her blood results show a normal ESR, CRP, FBC, a weakly positive ANA 1:80 and normal complement. Which is the most likely diagnosis? A : Polymyositis B : System lupus erythematous (SLE) C : Sjogrens syndrome D : Polymyalgia rheumatica E : Fibromyalgia.

A 58-year-old female presents complaining of right shoulder pain. She does not recall any prior injury butnotes that she feels that the shoulder has been getting progressively more stiff over the last several months. She previously had several episodes of bursitis of the right shoulder that were treated successfully with NSAIDs and steroid injections. The patients past medical history is also significant for diabetes mellitus, for which she takes metformin and glyburide. On physical examination, the right shoulder is not warm or red but is tender to touch. Passive and active range of motion is limited in flexion, extension, and abduction. A right shoulder radiogram shows osteopenia without evidence of joint erosion or osteophytes. What is the most likely diagnosis? A. Adhesive capsulitis B. Avascular necrosis C. Bicipital tendinitis D. Osteoarthritis E. Rotator cuff tear

A 45-year-old woman is admitted with a spiking temperature and sweats. She has been unwell for the last 3 weeks with flitting arthralgia and lethargy. There is a rash over her trunk which is most prevalent in the mornings. Blood cultures are sterile. Her recent transthoracic echocardiogram is normal. ESR 56mm/hour. Her ferritin is elevated at 6000(g/l. Autoimmune screen is negative. 1) bacterial endocarditis 2) systemic lupus erythematosus 3) rheumatoid arthritis 4) adult onset Stills disease 5) meningitis

A 60-year-old accountant complains of recurrent attacks of exquisite pain and swelling in the left big toe. Which of the following conditions is NOT likely to be associated with this disorder? A : Chronic alcoholism B : Obesity C : Rheumatoid arthritis D : Diabetes mellitus E : Diuretic therapy.

A 68-year-old woman with longstanding congestive cardiac failure (ejection fraction 20%) presents with a hot, swollen right knee. The following results are obtained: FBC normal, Urea 11mM, Creatinine 196ul. Synovial fluid: many monosodium urate crystals seen on microscopy, culture sterile. What is the best treatment for her acute arthritis? A : Allopurinol B : Colchicine 0.5mg every 2-4 hours C : Indomethacin 50mg tds D : Co-codamol 30/500 every 6 hours E : Intra-articular corticosteroids

A 34-year-old man presents with severe low back pain, which has forced him to stop work as a bus driver. He has had back pain on and off for many years, on occasion with right-sided sciatica. The pain used to be helped by rest, but is now present more or less all the time and is stopping him from sleeping properly. The most likely diagnosis is: A : mechanical back pain. B : ankylosing spondylitis. C : myeloma. D : osteoporosis. E : osteoarthritis.

Red flag symptoms, requiring urgent investigation to exclude sinister pathology, include: age >55 or <18 years progressive pain night pain systemic symptoms progressive neurological deficit past history of malignancy or immunosuppression recent trauma.

A 50 year old man presents with a 6 week history of general malaise and a 2 day history of a right foot drop, a left ulnar nerve palsy and a widespread purpuric rash. He complains of arthralgia but has no clinical evidence of inflammatory joint disease. Echocardiogram is normal, blood cultures are negative, ESR 100 mm/hr, ANCA negative, ANA negative, rheumatoid factor strongly positive, C3 0.8 g/l (0.75 - 1.6), C4 0.02 g/l (0.14 - 0.5). Dipstick urinalysis shows blood ++ but no protein. 1) ANA negative SLE 2) Cryoglobulinaemia 3) Infective endocarditis 4) Polyarthritis nordosa 5) Rheumatoid arthritis

 A patient with primary Sj grens syndrome that was diagnosed 6 years ago and treated with tear replacement for symptomatic relief notes continued parotid swelling for the last 3 months. She has also noted enlarging posterior cervical lymph nodes. Evaluation shows leukopenia and low C4 complement levels. What is the most likely diagnosis? A. Chronic pancreatitis B. Secondary Sj grens syndrome C. HIV infection D. Lymphoma E. Amyloidosis

A 64-year-old man with coronary artery disease an atrial fibrillation is referred for evaluation of fevers, arthralgias, pleuritis, and malar rash. The symptoms have developed over the past 6 months. The pleuritis has responded to steroid therapy, but prednisone has been unableto be tapered off due to recurrence of symptoms at daily steroid doses <15 mg of prednisone. His medications include aspirin, procainamide, lovastatin, prednisone, and carvedilol. At this stage antibodies directed against which of the following proteins is most likely to be positive? A. Cardiolipin. B. Double-strand DNA. C. Histone. D. Ribonucleoprotein (RNP). E. Ribosomal .

A 69-year-old woman with a 5-year history of intermittent left knee pain owing to osteoarthritis presents to your office 5 days after vacationing in Greece, where she developed increased knee pain and swelling. She says that she had been walking and climbing more than usual on this vacation. She and some of the vacationers in her group developed watery diarrhea around the same time, but there were no chills or fever. She had been treated with naproxen until 2 years ago, when she developed atrial fibrillation. She now takes acetaminophen as needed for knee pain and takes warfarin for the atrial fibrillation. Physical examination shows a temperature of 38 C (100 F). There is a large effusion in the left knee, with increased warmth but no redness. There is moderate tenderness and pain on motion, and she walks with a limp, which she did not have before. The other joints are unchanged. Laboratory studies Hemoglobin 13.7 g/dL Hematocrit 42% Leukocyte count 10,000/L Neutrophils 80% INR 2.1 Left knee radiograph reveals changes of osteoarthritis and an effusion. Which of the following would you do next? (A) Obtain stool culture and start treatment with ciprofloxacin. (B) Reduce warfarin dose and start treatment with celecoxib. (C) Order MRI of left knee. (D) Perform arthrocentesis. (E) Admit to hospital and start treatment with intra- venous ceftriaxone.

A 28-year-old woman presented with fatigue and extreme tiredness. Physical examination revealed facial skin rash and tenderness across the small joints of the hands. She was concerned that she might have systemic lupus erythematosus (SLE). Which of the following tests when NEGATIVE will virtually exclude the diagnosis of SLE? A : Antinuclear antibody (ANA) B : Anti-double stranded DNA (Ads-DNA) C : Anti-Sm antibodies D : Anti-histone antibodies E : Anti-Ro/SSA antibodies.

35. A 60-year-old-man complained of pain in both wrist evolving over 8 weeks. He noted swelling around that area but denied stiffness. On examination there was swelling and tenderness just proximal to the wrist joints without limitation of movement. There was also prominent finger clubbing. Radiographs revealed periosteal reaction over the lower end of the radius and ulnar. Each of the following disorders could be the cause behind this patient complain EXCEPT? A : Mesothelioma B : Bronchiectesis C : Diabetes mellitus D : Crohn's disease E : Whipple's disease.

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