T-score interpretation

Adult onset Still disease

- rare form of inflammatory arthritis
- begins after the age of 16 years 
- diagnosis of exclusion
- serum ferritin is usually elevated
- RF and ANA are classically negative
- treatment: NSAIDs
- Yamaguchi's criteria

Relapsing polychondritis

- characterised by inflammation of cartilage (ear, nose and laryngotracheobronchial tree)
- also manifested with scleritis, neurosensory hearing loss, polyarthritis, cardiac abnormalitis, skin lesion and glomerulonephritis
- most common in 5th decade
- systemic features such as fever, fatigue and weight loss precede the clinical signs by several weeks
- auricular chondritis is the most frequent presenting manifestation (40%), and eventually affecting 85% of patients
- typically involving pinna of ears and sparing earlobe because they do not contain cartilage
- treatment: prednisolone 40-60mg/day

Takayasu's arteritis

- an inflammatory and stenotic disease of medium and large-sized arteries characterized by strong predilection for the aortic arch and its branches
- a.k.a aortic arch syndrome
- 2-3 per million
- 80% are women and mean age of onset is 30 years
- panarteritis with inflammatory mononuclear cell infiltrates and occasionally giant cells
- presents with fever, night sweats, arthralgia, anorexia and weight loss
- pulses are commonly absent in the involved vessels, particularly subclavian artery
- hypertension occurs in 32-93% of patients and contribute to renal, cardiac and cerebral injury
- diagnosis is confirmed by the characteristic pattern on arteriography which includes irregular vessel walls, stenosis, post stenotic dilatation, aneurysm formation, occlusion and evidence of increased collateral circulation
- corticosteroid with the addition of steroid sparing agents such as methotrexate or azathioprine are mainstay of treatment

Henoch-Schonlein Purpura

- a.k.a anaphylactoid purpura
- small vessel vasculitis characterised by palpable purpura (usually over buttocks and lower extremities), arthralgia, gastrointestinal signs and symptoms and glomerulonephritis
- presumptive pathogenic mechanism for HSP is immune complex deposition (usually IgA)
- palpable purpura is seen in virtually all paediatric patients
- gastrointestinal involvement is characterised by colicky abdominal pain associated with nausea, vomiting, diarrhea or constipation frequently accompanied by passage of blood and mucus per rectum, bowel intussusception may occur
- diagnosis of HSP is based on clinical signs and symptoms
- skin biopsy : leukocytoclastic vasculitis
- excellent prognosis, 1-5% of children progress to ESRF
- treatment: prednisolone (1mg/kg) has been shown to be useful in decreasing tissue edema, arthralgia and abdominal discomfort
- patients with rapidly progressive glomerulonephritis have been anecdotally reported to be benefit from intensive plasma exchange combined with cytotoxic drugs

Human leukocyte antigen (HLA)

- found on chromosome 6
- HLA corresponds to MHC class I (A,B and C)
- HLA corresponds to MHC class II (D)

HLA associations
- HLA DR2 : SLE
- HLA DR3 : autoimmune hepatitis, Sjogren syndrome
- HLA DR4 : Felty syndrome
- HLA DQ2 / DQ8 : coeliac disease
- HLA B27 : AS, Reiter's syndrome
- HLA Cw6 : psoriasis
- HLA B8 : myasthenia gravis
- HLA B5 / B51 : Behcet's disease

X-linked hypophosphataemic rickets

- dominantly inherited (transmitted by affected father to all daughter)
- defect in renal phosphate handling 
- mutation in the PEX or PHEX genes which encode an endopeptidase
- rickets develops in early childhood and is associated with poor growth
- low phosphate, high PTH, high urine phosphate
- treatment: high dose oral phosphate and vitamin D (calcitriol)

Familial mediterranean fever (FMF)

- autosomal recessive
- MEFV gene on chromosome 16 codes for pyrin/marenostrin (activate biosynthesis of chemotactic factor inactivator in neutrophils)
- recurrent attacks of fever, arthritis, serositis, pericarditis, peritonitis
- raised inflammatory markers
- associated with AA amyloidosis causing nephrotic syndrome
- treatment: colchicine

Inclusion body myositis

- idiopathic inflammatory myopathy occur usually in men over 50 years
- gradual muscle weakness (mainly distal)
- weakness finger/wrist flexors out of proportion to finger/wrist extensors and shoulder abductors and weakness of knee extensors disproportionate to the hip flexors (quadriceps and long finger flexors)
- weakness of pharyngeal muscle causes dysphagia in 50%
- mild CK elevation
- muscle biopsy: inflammation and basophilic rimmed vacuoles with diagnostic filamentous inclusions and vacuoles on EM
- IBM is refractory to steroid and immunosuppresive agents

Juvenile idiopathic arthritis

- persistent oligoarthritis is the most common form of JIA (50-60%), four or fewer joints are affected (knees, ankles and wrist). Uveitis is common with positive ANA and seen in younger girls (peak at 3 years old)
- polyarticular JIA affects older girls. 2 forms - rheumatoid factor positive or negative
- Still's disease presents with high fever, evanescent pink maculopapular rash with arthralgia, arthritis, myalgia and generalised lymphadenopathy. Autoantibodies are negative
- enthesitis related arthritis usually affects teenage boys, causing asymmetrical lower limb arthritis associated with HLA-B27 and risk of iritis

DMARDs side effects

Methotrexate

- marrow suppression, hepatic fibrosis, pneumonitis

Sulfasalazine

- leukopenia & thrombocytopenia, rash and macrocytosis

Hydroxychloroquine

- retinopathy

Gold 

- given by IM

- pancytopenia, lung fibrosis, cholestatic jaundice, glomerulonephritis, angioneurotic edema, exfoliative dermatitis

Penicillamine

- drug-induced lupus, proteinuria, loss of taste, pancytopenia

Leflunomide

- diarrhea, nausea, alopecia, rash

Cryoglobulinemia

- cryoglobulins are immunoglobulins and complement components which precipitate reversibly in cold, which leads to small vessel damage and deposition on the wall of small vessel result in generalised vasculitis
- presents with purpura, arthralgia, leg ulcers, Raynaud's phenomenon, polyneuropathy, asymptomatic proteinuria, microscopic hematuria or nephrotic syndrome
- skin most commonly involved (>90%) - reticulated skin pattern of microthrombosis and areas of gangrene
- management : plasma exchange, high dose steroid, chemotherapy (cyclophosphamide) and treatment of underlying conditions
- 3 types are recognised

Type I
- monoclonal antibody (usually IgM)
- associated with multiple myeloma and lymphoproliferative disorder
- presents with acrocyanosis, Raynaud's phenomenon, retinal hemorrhage

Type II & III (mixed cryoglobulinemia)
- IgM or IgA with rheumatoid factor activity binds to polyclonal IgG
- type II is monoclonal ; whereas type III is polyclonal
- presents with glomerulonephritis (more common in type II), vasculitic rash and Raynaud's
- they can activate the classical pathway of complement and cause consumption therefore low C4 with normal C3
- associations: Hepatitis B and C, HIV, CMV, malaria, EBV, malaria, autoimmune disorder
  * Meltzer's triad =  Purpura + Arthralgia + Myalgia *
     (Typically seen in polyclonal CG - hepatitis C)

Autoantibodies

- dsDNA : SLE

- anti-histone : drug-induced lupus

- anti-centromeric : limited scleroderma

- anti-Ro (SS-A) : SLE, primary Sjogren (anti-Ro only= SLE)

- anti-La (SS-B) : SLE, primary Sjogren

- anti-Sm : SLE

- anti-RNP : SLE, MCTD

- anti-Jo : polymyositis, dermatomyositis

- anti-Scl70 (topoisomerase 1) : diffuse scleroderma

Erosive osteoarthritis

- A form of OA marked by greater degree of inflammation and characterised by presence of erosions on plain radiograph
- predominantly affects postmenopausal women
- classically affects PIPJ and DIPJ
- gull's wing or inverted T pattern of erosion is typical
- commonly confused with RA, but there is no juxtaarticular osteoporosis

Gonococcal arthritis

- commonest cause of septic arthritis in previously young fit adult
- more common in females and homosexual men
- presents with fever, characteristic rash/pustules, polyarthralgia and tenosynovitis, followed by large joint monoarticular arthritis.
- treatment: IV ceftriaxone, examination of joint and washout under anaesthesia

Retroperitoneal fibrosis

- a.k.a Ormond's disease
- more common in males and peak in 5th or 6th decade of life
- one of the multifocal fibrosclerotic syndrome (which involves mediastinal fibrosis, sclerosing cholangitis and Riedel thyroiditis)
- presents with low back pain (commonest), malaise, anemia, uremia (ureteric obstruction), raised ESR
- 2/3 idiopathic, associated with malignancy, drug (methysergide, practolol), radiotherapy, untreated AAA, SLE, scleroderma, carcinoid syndrome
- CT is best diagnostic modality
- treatment: steroid, azathioprine

Wegener's granulomatosis

- granulomatous necrotizing vasculitis
- triad of
  i) upper airways (granuloma) - rhintis (first sign), epistaxis, sinusitis, saddle nose (perforated septum), otitis, mastoiditis
  ii) lungs (granuloma and vasculitis) - multiple pulmonary nodule (coin lesions), cavitating lesion with diffuse alveolar changes, presents with hemoptysis
  iii) renal (vasculitis)- segmental crescentric necrotizing glomerulonephritis
- c-ANCA (PR3) positive (highly sensitive and specific)
- treatment: IV methylprednisolone, cyclophosphamide





Poor prognostic indicators
- presence and severity of renal involvement
- elderly
- pulmonary hemorrhage
- poor response to therapy at 2 weeks
- high degree of sclerosed glomeruli/interstitial scarring on biopsy

Felty's syndrome

mnemonic : "SANTA"

S: Splenomegaly
A: Anemia
N: Neutropenia
T: Thrombocytopenia
A: Arthritis (Rheumatoid)

- up to 3% of RA patients have Felty's syndrome
- 90% patients with Felty's syndrome are HLA DRW4

Arthritis mutilans

- rare form of psoriatic arthritis, found in 1-5% of patients
- resorption of bone (osteolysis) with dissolution of joint
- redundant overlying skin with a telescoping motion of joint
- X-ray: pencil-in-cup
- treatment: methotrexate

systemic vasculitis

Large vessels
- Takayasu's arteritis
- Giant cell arteritis

Medium vessels
- Kawasaki disease
- classical PAN

Small vessels
- Churg Strauss syndrome
- Wegener's granulomatosis
- Microscopic polyangitis
- Henoch Scholein purpura
- Essential cryoglobulinaemia