Rheumatology Study Notes

Rheumatology / Orthopaedics Bone development and structure Bone tissue develops from mesenchyme – evident at 8/40 Metaphysis = distal, flared portion of bone Epiphysis = growth plate Diaphysis = shaft Bone growth is stimulated by testosterone, thyroxine & growth hormone Testosterone eventually causes fusion of epiphysis Causes of delayed bone age Delayed puberty Hypopituitarism GH deficiency Hypothyroid Steroid therapy Chronic illness Causes of advance bone age Precocious puberty CAH Screening tests: Walk on toes & heels Sit cross legged on floor then jump up Arms extended straight forward and make fist Full wrist extension (saying prayers) Raise both arms straight above head Turn head to look over both shoulders Also look at Gait, rashes, swelling, range of movements Neonatal / developmental problems Hands Syndactyly = fusion Polydactyly = extra digit Ectrodactyly = lobster claw Talipes Equinovarus 1/1000 (m:f = 2:1) Can be isolated defect or assoc with neuromuscular problems 20% risk if FH Male : female = 3:1 50% are bilateral Can be due to severe oligohydramnios, neuromuscular disorder or malformation syndrome Ankle in equinus, hindfoot in varus Positional talipes foot can be fully dorsiflexed Rx – Manipulation & strapping (Ponsetti) Can required Achilles tenotomy Talipes Calcaneovalgus 1/10,000 Dorsiflexed & everted More amenable to simple manipulation Convex pes valgus (vertical talus) Forefoot abducted & dorsiflexed Assoc with chromosome problems Requires surgery Other Foot deformity – e.g. metatarsus varus. No evidence that affects walking, but will lead to abnormal callus formation and problems with shoes Genu varum (bow legs) Outward curving of tibia Usually corrects with growth Genu valgum (knock knees) Usually innocent if symmetrical & no other abnormality If severe ? rickets Genu recurvatum (right) Hyperextensible knees In severe cases can dislocate On lateral XR tibia is anterior to femur Pes Planus (flat feet) Usually with ankle varus Generally improve with age Orthosis can decrease pain and increase posture Scoliosis = severe curvature of the spine Postural scoliosis corrects with correct posture & won’t be structurally abnormal Structural scoliosis is due to vertebral defects due to failure of formation (hemivertebra) or failure of segmentation (unsegmented bars). 20% will have GU anomalies therefore all need renal US Idiopathic adolescent scoliosis = 80-85% of all structural scoliosis Mainly girls 10-14ys Arthrogyrposis multiplex Multiple joint deformities involving more than one limb Can occur in neuromuscular (e.g. congenital dystrophy, SMA), oligohydramnios or bicornate uterus Developmental Dysplasia of the hip Terminology Stable = no abnormal movement Click = heard / felt, usually ligament laxity & in up to 10% of infants Dislocatable = in joint, but dislocates on Barlow’s Dislocated = out of joint to start with, confirm with Ortolani Incidence & risks 1-2/1000 90% are dislocatable, 10% are dislocated Left 4x more common than right Assoc with FH (risk 1/30), presentation (breech = 14%), Gender (f:m = 6:1), Race (increased in Italy, decreased in china), Nerve / muscle probs (e.g. spina bifida, hypertonia, hypotonia), syndromes (T13, 18 etc), other congenital anomalies Is the hip in joint? – inspect gluteal folds, legs equal length, test hip abduction – if not to fully then dislocated Is the hip stable? = Barlows – Adduction & downward pressure to posterior dislocate Can a dislocated hip be relocated? = Ortolani Assesses if hip is already dislocated Lift – to bring femoral head from dislocated posterior position to opposite acetabulum AND simultaneously abduct to reduce the femoral head over the posterior acetabulum lip If +ve then “clunk” felt as relocated Ix – US hip – for all instability, FH, Breech & assoc abnormalities Rx- Principle is to keep hip immobilised in abducted position for 2-3 months to allow acetabular rim to develop & ligaments to strengthen No place in modern day for “double nappies” Pavlik harness / Von Rosen splint If not diagnosed until 4/12 old then needs 2/52 traction fb surgery Complications – AVN Neonatal Dwarfism Primordial Severe growth retardation at birth BUT no selective shortening e.g. Russel-Silver, Cornelia de Lange, Conradi, Seckel’s (bird head), Cockayne, leprechanism and progeria Chondrodystrophic (skeletal dysplasia) Disproportional shortening of limbs Often assoc with other abnormalities e.g. cleft lip, polydactyly, DDH, & dysmorphism Most common syndromes are: Achondroplasia (see right upper) 1/150000, 80% are new mutations FGFR3 gene = AD Shortening of limbs with extra skin creases Low nasal bridge More in proximal bones = femur & humerus. Enlarged head, normal trunk, short limbs. Hearing problems common Asphyxiating thoracic dystrophy Thanatophoric dwarf (death bearing) Bones fail to extend (see right) Diastrophic dwarf Ellis-van Creveld Syndrome VACTERL (aka VATER) (diagnose if 3 of the following) Vertebral anomalies 70% – hypoplastic vertebrae / hemivertebrae. Can à scoliosis Anal 55% – atresia / imperforation à early surgery Cardiac 75% - most commonly VSD / ASD / Fallots, less commonly truncus arteriosus / TGA Tracheo-oEsophageal 70% - atresia with trachea-oesophageal fistula Renal 50% - reflux / aplasia / dysplasia. Also assoc with single umbilical artery Limb probs 70% - Radial aplasia, hypoplastic thumb, polydactyl Differentials for swollen, painful joint Juvenile Arthritis Inflammatory – IBD, sarcoid, CF, autoimmune hepatitis Haematological – leukaemia, lymphoma Malignant – neuroblastoma Reactive – post strep, Rheumatic Fever, post enteric, post viral Infection – septic arthritis, osteomyelitis, TB, Lyme disease Bacteria – Monoarthritis à S.pyogenes Polyarthritis à campylobacter, rat bite fever Post infectious e.g. reiters, gonococcus, M.TB Immunocompromised – e.g. aspergillus, mycoplasma Direct virus – e.g. mumps, rubella, 5th disease, Hep B Irritable hip / discitis Systemic – SLE, vasculitis, juvenile dermatomyositis, scleoderma Downs Arthritis Mechanical – Osgood schlatter, chrondromalacia patella, schevermann disease, hypermobility, “growing pains” = nocturnal idiopathic pain syndrome, skeletal dysplasia, collagen diseases (ehlers danlos, Marfan’s, stickler, storage diseases, AVN, Perthes, SUFE, Trauma (accidental / NAI), haemophilia / sickle cell, rickets, DM, Tumour – osteoma, haemangioma, sarcoma, rhabdomyosarcoma, ewings Psychological – idiopathic, fibromyalgia Infection Septic arthritis = surgical emergency Most commonly Staph aureus (75%) / pyogenes / S.pneumonia / GBS Usually spread in blood & settles in metaphyses Sx – systemically unwell, fever, headache, joint pain, decreased ROM, unwilling to wt bear Dx – if pyrexia > 38.5 and unable to wt bear = 99% certain. Also raised ESR & WCC Ix – X-rays of little use (osteopenia + joint space narrowing on XR) Need to aspirate + blood cultures Osteomyelitis Usually affects metaphyses (growth plate acts as barrier) Usually comes from bacteraemia Usually sub-acute presentation (pyrexia, erythema, tender) Only 60% will be B.Cult +ve 90% = S.Aureus, staph pyogenes, also strep pyogenes (salmonella in sickle cell) Sx – night pain, immobility Ix – X-ray – if late then appears moth eaten and periosteal reaction Rx – immobilise, high dose Abx Sequestrum = necrotic nidus Involucrum = cloak of new bone around the infected area TB Usually secondary to pulmonary TB Can cause reactive arthritis, or Potts (vertebral) Diagnose by PCR Treat as per adult Reactive arthritis Asymmetrical lower limb +/- dactylitis Usually settles in 3-6 wks May also benefit by clearing remaining causative organism (e.g. Chlamydia) Rheumatic fever – post streptococcal Reiter’s Syndrome – urethritis, arthritis & conjunctivitis Post enteric / GU infection – commonly shigella, salmonella, yersina or chlamydia. HLA B27, commoner in boys. Rx with NSAIDs Lymes disease Spirochaete (Borrelia burgdorferi) = tick vector Rash, fever, erythema chronic migrans (picture), episodic arthritis, meningitis, encephalitis, uveitis) If untreated can later cause encephalitis Transient Synovitis (irritable hip) Commonest cause of limp & hip pain in young children Often follows mild URTI 3-10 yrs (peak 6 yrs, boys) Sx Sudden onset with limp & pain Hip held in flexion and external rotation Ix ESR normal / mildly raised WCC normal Effusion on hip US Diagnosis = of exclusion Rx Aspirate to exclude infection and reduce pressure Analgesia & NSAIDs Resolves in 7 days Discitis Acute, self-limiting, peak 1-3 yrs, back pain & stiffness Juvenile idiopathic Arthritis = Stills Disease Under 16 yrs old Lasting > 6 wks 5-18 / 100,000 children G:b = 2:1 Peaks at 1-3 yrs oligoarthritis g>b and 9 yrs b>g Definition for diagnosis: Onset < 16 yrs Synovitis (swelling, pain, decreased ROM, morning stiffness) For 6+ weeks Sx Joint stiffness & gelling – esp. early morning Disuse atrophy Limb length discrepancy (femoral condylar hypertrophy) – affected limb initially grows faster due to stimulation of growth plate regions. But will fuse faster à overall shortened Tiredness & lethargy Macular rash Iridio-cyclitis Classification Systemic = Still’s disease = 10%, Peak 5yrs Can precede joint problems Evening spikes of temperature, subnormal dips in mornings Salmon rash to trunk, axillae & inner thighs at height of fever Lymphadenopathy, splenomegaly, serositis, pallor Oligoarthritis - 50% Up to 4 joints affected. Often with uveitis, especially common in ANA +ve girls Persistent – continues in > 4 joints throughout disease Extended - > 4 joints in 1st 6 months = poor prognosis Polyarthritis RF neg = 5+ joints in 6m but –ve RF RF pos = 5+ joints in 6 months & +ve RF within 6 months of that Enthesitis related – boys > 8 yrs. Usually +ve HLA B27. Asymmetrical large joints, lower limbs mainly. Spine involvement is rare & can à Ank Spond in teens Psoriatic – arthritis + psoriasis (or FH of psoriasis), asymmetrical disease, dactylitis Management Exclude Sepsis NSAIDS, Steroids If polyarthritis à methotrexate, sulfasalazine (if GI related) Growth Inflammation, immobility and steroids all reduce growth and bone mass Inflammatory arthritis à elongated limbs, overgrowth around joints and advanced bone age NB wrist arthritis à inaccurate bone age Arthritis in Jaw à TMJ fusion à micrognathia & overbite (if unilateral à facial asymmetry 50% of JIA have protein-energy malnutrition (due to increased energy req) Uveitis Asymptomatic, but leads to progressive loss of vision. Commonest in young JIAs Good prognosis if treated early, otherwise significant morbidity ALL children with JIA should have 6m slit lamp examination until 12 yrs old or disease activity reduces Highest Risk in ANA +ve and oligoarthritis Rheumatology Markers Anti Nuclear Antibody (ANA) Non specific – but is very sensitive (a negative ANA excludes SLE) 5% of normal ppn are +ve Rheum – SLE, dermatomyositis, sjogrens, sleroderma, vasculitis, JIA Drugs – carbemazepine, isoniazid, sulfasalazine, chlorpromazine Hepatic – autoimmune,PBC Pulmonary – idiopathic fibrosis, primary pulmonary HTN Infection – transient +ve with acute infection, long term +ve if chronic Malignancy – lymphoma, leukaemia Haem – ITP, autoimmune haemolytic anaemia Others – DM, end stage renal failure, post organ transplant ANCA Anti Nuclear Cytoplasmic Antibody Perinuclear – p-ANCA à glomerulonephritis, UC, CAH & HSP Diffuse – c-ANCA à Wegners and Kawasaki disease Both found in HIV & Crohns dsDNA Ab Very specific for SLE but is negative in 50% of SLE = not very sensitive More likely to be positive in renal and cerebral involvement Relates to disease activity – decreases if managed well Rheumatoid Factor In response to inflammatory stimulus therefore +ve after infection +ve in 5% of JIA (tend to be girls > 10yrs with severe disease) HLB B27 ( Human Leucocyte Compatibility antigen ) +ve in 10% of normal population Strong assoc with psoriatic arthropathy (20% +ve) Enthesitis related arthritis (95%) IBD (50%) Reiters syndrome (80%) Anterior uveitis (50%) Autoimmune disoders IBD Failure to thrive, decreased energy even when no arthritis 2 patterns seen Large joint (knee & ankle) – responds well to bowel treatment Progressive spinal Ank Spond – continues irrespective of bowel involvement Sarcoidosis (rare) Florid symptoms, limited effect on pain & movement Assoc with uveitis, erythematous skin rash (can present as erythema nodosum) Juvenile Dermatomyositis 80% ANA +ve Vasculitis à decreases capillary: muscle fibre ratio 2 age peaks – toddlers & young schools (5yrs) then teens (14 years) 50% are acute onset Sx Proximal myopathy – difficult walking, climbing stairs Myalgia with non destructive arthritis Loss of gross motor milestones Gottron’s Papules – redness à scaring over MCPJ, PIP, DIP & extensor surface of knee, ankle and elbow Also extensor erythema over distal joints Malar erythema with heliotrope rash – purple telangectasia on eyelids. PHOTOSENSITIVE Nail fold capillary infarcts & dilatation Untreated à striated then smooth then GI tract then heart muscle affected Also Ca deposits over bony prominences, subcutaneous tissue & fascia (will improve with aggressive treatment) Can progress very quickly à resp failure & loss of swallowing Dx – raised CK & ALT, history, muscle biopsy with perivascular lymphocytic infiltrate. Characteristic changes on EMG, ANtiJo-1 Ab Rx – 6-12 month course of steroids. If very severe give methotrexate / ciclophosphamide SLE 0.8/100,000 – increases to 12 / 100,000 in teenage girls Most common in Afro-Caribbean, then Asians, then white Neonatal SLE Transient passage of maternal Anti-Ro IgG to baby. Mum can be asymptomatic. Baby presents with congenital heart block, can also have vasculitic rash to face (well defined small areas) Childhood SLE Mucocutaneous – 50% have butterfly rash, discoid scars, photosensitivity, vasculitis fingers & toes, painless palate ulcers, Raynaud’s, livedo-reticularis MSK – non erosive arthritis, myositis, tenosynovitis Neuro – CVA, peripheral neuropathy, psychosis, seizures, encephalopathy Haem – persistent lymphopenia, neutropenia, autoimmune haemolytic anaemia, thrombocytopenia Immune – ANA, dsDNA, Anti Smith, raised IgG Renal – glomerulonephris, nephritic syndrome Serositis – pleurisy, pericarditis, small effusions Others – hepatosplenomegally, fever, lymphadenopathy, wt loss, anorexia, raised ESR with normal CRP Treatment – steroids & immunosupressants (e.g. cylophosphamide / methotrexate / hydroxycholorquine. NSAIDs can help arthritis. Should use sunblock Systemic Scleosis / Scleroderma Multisystem involvement – difficult to control, poor outcome Early Raynaud’s, oedema à skin tightening, waxy, hard skin à contractures, telangectasia & calcinosis over extensor surfaces, sicca (dry eyes, mouth etc), arthritis, bone infarcts, decreased finger pulps, GI reflux & dysphagia. If pulmonary / cardiac / renal involvement = poor prognosis Rx with immune suppression HSP Most common vasculitis affecting skin 14-25/100,000, usually under 14 yrs (more common in younger) Peak 5 yrs. ? Triggered by URTI Multisystem Rash = vasculitis over legs & buttocks, can start with urticaria 60-85% affects joints (esp. knee & ankle), GI tract (pain + GI bleeds) & kidneys 1% of renal involvement à end stage renal failure (= 15% of dialysis patients) If glomerulonephritis then use cyclophosphamide & plasma exchange Usually manage conservatively but can use steroids Resolves in 2-3 weeks Kawasaki (aka Mucocutaneous Lymph Node Syndrome) 2/100,000, 2/3 of cases are < 5yrs More common in Far East / Japanese Autoimmune necrotising vasculitis affecting medium & small vessels Features Fever (100%) – often > 40 degrees and no response to Abx but will respond to antipyretics Misery (100%) – likely due to aseptic meningitis Downs Oral (90%) – strawberry tongue, fissured lips, erythema of oropharynx Conjunctivitis (85%) – bilateral, non purulent Rash (80%) – polymorphous over hands, trunk & perineum Lymphaedenopathy (70%) – with nodes > 1.5cm Extremities (70%) – oedema à desquamation Cardiac – myositis à arhythmia & CCF, pericarditis & coronary artery aneurysms after 2-3 weeks (Echo at 6/62) à can cause sudden death Diagnosis Fever for > 5 days AND 4 of the 5 following criteria • Bilateral non suppurative conjunctivitis • Mucous membranes (1 or more) of pharyngeal injection, dry fissured lips, injected lips, and "strawberry" tongue • Extremities (1 or more) peripheral erythema, peripheral oedema, periungual desquamation, and generalized desquamation • Polymorphous rash, primarily truncal • Cervical lymphadenopathy >1.5 cm in diameter Prognosis worse in younger children (esp with cardiac manifestations) Rx includes IvGammaGlobulin & high dose aspirin to reduce risk of cardiac manifestations (reduces risk from 20% to <5%). Low dose aspirin long term reduces risk of thrombosis Hypermobile. Can à inflammatory arthritis. Poorly responsive to steroids / immune suppression Mechanical Enthesitis Enthesitis = point of insertion of tendon / ligament / fascia into bone Prone to physical stresses and inflammatory stress e.g. plantar fasciitis e.g. Achilles tendonitis e.g. Osgood-Schlatter Painful, tender swelling of tibial tubercle Due to repeated minor avulsion trauma at insertion of patellar tendon Rx – some response to NSAIDs, some avoidance of sport, some immobilisation Resolves at skeletal maturity Slipped Upper Femoral Epiphysis (SUFE) Early teens, 10-14 F, 12-16 M ? Related to rapid skeletal growth, more common if obese Assoc with hypothyroid, radiotherapy, CRF and growth hormone treatment Can be acute or insidious onset 20% will slip bilaterally Hip pain often referred to knee Rx with percutaneous pinning Legg-Calve-Perthes 4-8 yrs (b:g = 5:1) Necrosis of femoral epiphysis à Painless limp, thigh atrophy & short stature Can take several years for bone to renew à disability & deformity & OA Better prognosis in younger boys over older girls Anterior knee pain Up and down stairs / after sitting / bending knees for long time à difficult straightening with crepitus. Pain is reproduced by pressure on patella Pain does not correlate to cartilage damage Improves with age Chondromalacia Patellae Softening of articular cartilage of patella due to indirect trauma Retropatellar pain worse on rising after prolonged sitting / stair climbing Crepitus Rx – avoid repeated knee bending, minimise high impact sport Stress # Repeated activity in weight bearing areas Exacerbated by exercise Often affect foot – metatarsal shaft, navicular or calcaneum Shin Splints Pain on anterior shin, numbness of 4th toe, increase by activity, improves with rest. Overuse of posterior tibial muscle. Rx by activity modification Nocturnal idiopathic pain (growing pains) 3-10 yrs, awake at night with leg pain. Rx with massage / simple analgesia. Hypermobility Common normal finding. More common in girls & afrocarribeans à good at ballet & gym. If cause problems à delayed walking & hypotonia. Pain after exercise, Encourage continued mobility Marfans AD - Defect in Fibrillin (found in collagen) 25% are spontaneous mutations 4-6 / 100,000 Tall but arm span > height. High arched palate Arachnodactyl( long thin bones) Hypermobile joints, ocular abnormalities (lens subluxation & severe myopia) +ve Steinburg sign = thumb extends beyond folded fist Complications: CVS – aortic root dilatation & dissection, aortic & mitral regurgitation Eyes – up & out lens dislocation, myopia, retinal detachment Thorax – pneumothoraces, kyphoscoliosis Increased incidence of recurrent / incisional hernia Homocysteinuria AR - defect in cystathionine B synthase Similar phenotype to Marfans Osteoporosis Down & medial lens dislocation Increased arterial thrombosis & learning difficulties Diagnosis by plasma & urine AAs. (high homocysteine in urine, high methionine in plasma) Ehler’s Danlos (aka Cutis hyperelastica) Defect in the synthesis of collagen (usually Type I and III) Highly flexible joints, prone to dislocation High, narrow palate Fragile blood vessels (due to cystic media necrosis) à aneurysm & easy bruising Velvet smooth skin, stretchy & abnormal wound healing Valvular heart disease Cohen Kabuki Developmental delay Microcephally Hypotonia Also myopia, retinal dystrophy, hypermobility Thick hair & eyebrows, long eyelashes, down slanting eyes, short philtrum, prominent upper central teeth 30% congenital heart defects 50% renal tract anomalies, 50% hearing loss, hypotonia, postnatal growth deficiency (83%). Hypermobility Unusually sociable, like routine, happy disposition, delay in fine motor & speech skills Moriquo’s (aka Mucopolysaccharidosis IV) AR mucopolysaccharide storage disease – accumulation of keratin sulphate Usually recognised at 1-3 yrs Corneal clouding, aortic valve disease, urinary excretion of keratin sulphate Hypermobility, large fingers, valgus knees, wide spaced teeth, bell shaped chest, dwarfism Stickler AD, rare. Affects collagen formation (defect concerns hyaluronic acid) Flattened face appearance – underdeveloped midface bones. Pierre Robin is common. Micrognathia, cleft / high palate, Severe myopia, high risk retinal detachment & blindness Destructive painful arthropathy with hypermobile joints Seckel (aka microcephalic primordial dwarfism) Defects on Cr 3 & 8 IUGR Postnatal dwarfism is small head, narrow, bird-like face, beak nose, large eyes, receeding mandible & mental retardation Metabolic Muscle pains Glycogen storage diseases McArdle Disease (GSD V) Defect in glycogen metabolism - Deficiency of Myophosphorylase (converts Glycogen to G6P) 1 / 100,000 Features Pain starts within approx 3min of starting activity If ease off slightly à Improves after 7-10 minutes = mobilisation of other fuel through oxidation of fatty acids = 2nd wind If don’t ease off à cramps & contractures similar to rigamortis à Rhbdomyolysis Sx myoglobinuria in 60% (colour variations from tea to Guinness) ARF in 10% Weak & muscle wasting in 20% Ix CK (not during crisis) can be 500 - 6000 Muscle biopsy – 6-8 weeks post attack otherwise false –ves Screen for 2x genetic markers Rx Avoid eccentric (anaerobic) exercise Pace any activity Gentle regular exercise GSD 7 Also assoc with haemolytic anaemia & gout GSD 9 Assoc with liver disease Fatty acids oxidation defects e.g. VLCADD / CPT2 deficiency Features Hypoglycaemia in infants Unable to do prolonged exercise No 2nd wind Myoglobinuria Rx Avoid fasting High carb, low fat diet Glucose loading before, during & after activity Rescue glucose treatment for intercurrent illness Tumours 10-50% of paediatric haem malignancy and 15-25% of neuroblastoma have MSK features Haem malignancy - Usually oligoarthritis (commonest in knee), with pain localising to metaphysial region Neuroblastoma - Commonest cause of bony mets in children with fever & rash Bone tumours (rare) - Often diagnosed late, usually benign. Present with boring / aching pain, mass, path #, effusion if near joint, wt loss, fever, anaemia etc Simple cyst - Humerus or femur usually. Predispose to #. Rx with steroid injections Fibrous cortical defect - Usually found incidentally, observe, will usually self resolve Langerhans Cell Histocytosis – can be solitary or multiple lesions. Can also have systemic involvement e.g DM. Bone lesions will heal after biopsy Fibrous dysplasia – 1 or more bones, can à progressive deformity, excise & stabilise McCune Albright Skeletal developmental anomaly of bone forming mesenchyme M=F Medullary bone replaced with fibrous tissue Radiolucent with ground glass appearance Increased risk of precocious puberty, thyrotoxicosis, acromegally & Cushing’s Ewing’s tumour – 30x more common in whites than blacks Favours femur Systemic unwell, pain and mass, can have fever & path #s HIGHLY malignant Give neo-adjuvant chemotherapy and resect Osteosarcoma – Pain, mass and path fracture. Mets to lungs. Give neo-adjuvant chemotherapy and resect Osteolytic foci Can be histiocytosis X (eosinic granuloma), leukaemia, wilms, osteomyelitis etc Osteochondroma Most common benign bone tumour Outgrown (exostosis) capped with cartilage occurring close to growth plates (and pointing away from them). Grow with growth spurts and stop with skeletal maturity Can cause deformity of the bones “Hereditary exostosis” = Multiple AD, 1/50,000 people, 96% penetrance Usually diagnosed approx 3 yrs old 5-10% malignancy risk Endochondroma Most common benign cartilage tumour Lytic lesion (cartilage proliferation) within bone. Most commonly phalanges & metacarpals/tarsals (can affect other long bones). Most common 10-20 yrs (enlarge with growth spurts). Often asymptomatic (incidentally on x-ray) / as path fracture Endochondromatosis a.k.a Ollier disease (multiple endochondromas) has 25% lifetime risk of malignancy. Palpable masses, growth deformity and angulation. Manifests early childhood (once weight bearing) Maffucci syndrome – enchondromas + haemangiomas (as blue coloured soft nodules on skin), manifests in early childhood / puberty Osteoid Osteoma Benign tumour of late teens & early adulthood, more common in men < 1.5cm in diameter Most common in femur, tibia & vertebra X-ray shows radiolucent lesion with dense rim (bulges out) Pain relieved by aspirin is almost diagnostic Local surgery is curative Psychological Localised idiopathic pain syndrome Also known as reflex sympathetic dystrophy, algodystrophy, complex regional pain syndrome, sudeks atrophy History of supposed trauma à pain worsens with time Colour & temperature changes to limb à allodynia, no benefit from analgesia, worsen if splinted. Causes function problems – unable to dress, school etc Pain amplification syndrome e.g. fibromyalgia Disturbed sleep, +ve fibromyalgia points, IBD, tension headaches, anxiety, depression Can co-exist with DM / genuine arthritis etc Can be linked to abuse / psychological trauma Treat with exercise, reintegration, psychotherapy Calcium, Vit D and bone Osteoblasts = synthesis, Osteoclasts = absorption Growth occurs at metaphysic, end = epiphysis Bone growth Cartilage (chrondrocytes) proliferation Hypertrophic differentiation of chondrocytes Matrix formation Invasion by vessels Calcification Trabeculae formation Calcium 99% is held in bone Plasma Ca should be 2.2-2.6 Low Ca à high PTH (Chr 11q)à increased absorption from bone, increase renal reabsorption and increase PO4 excretion, increased GI absorption Calcitonin (Chr 11q) antagonises PTH Vitamin D – precursor in diet, converted in skin with UV light à hydroxylated in liver & kidney à increased intestinal absorption and mobilises bone calcium Hypocalcaemia < 2.2 mmol/l (symptoms generally occur < 2.0) Causes PTH deficiency (aplasia, mutation, autoimmune) Vit D Deficiency Mg2+ deficiency PO4 excess Sx – paraesthesia (mouth and hands), muscle cramps, carpopedal spasm, mood change, diarrhoea, convulsions, dry skin, coarse hair, brittle nails, enamel hypoplasia. Chvostek sign – taping over parotid à facial twitching Trousseau sign – 2/3 minutes with BP cuff inflated à wrist and finger flexion Ix – blds for Ca, Mg, PO4, ALP, PTH & Vit D Rx – oral supplements. If severe à IV calcium gluconate Renal osteodystrophy Decreased gut ability to absorb Ca Proximal myopathy assoc with Vit D Def à low Ca & high PO4 Raised ALP Leads to secondary hyperparathyroid Hypercalcaemia Ca > 2.65 Sx - Anorexia, polyuria, polydipsia, mood change, abdominal pain, constipation Also raised plasma Cr secondary to renal failure Causes – surgery / high Ca diet Hypoparathyroid Congenital – linked with DiGeorge syndrome Acquired – usually autoimmune Rx with Vit D Metabolic bone disease of prems (rickets of prematurity) In prems skeleton is mostly cartilage Ossification requires supply of calcium, phosphate & vitamin D (+ trace metals) TPN doesn’t contain sufficient Ca & PO4 to meet requirements Preterm formula & supplements help Immature liver & kidney have impaired ability to hydroxylate vit D à increase Vit D supplements If < 28 weeks likely to deficient in Copper Without supplementation of above à osteopenia, fractures & rickets appearance on x-rays Diagnosis – low serum phosphate is earliest marker à supplement Steroids & Diuretics (for CLD) worsen matters Rickets (osteomalacia) Failure to calcify the matrix and excessive accumulation of un-calcified cartilage & bone matrix (osteoid) Causes – X Linked Hypophosphataemic rickets (Vitamin D Resistant Rickets) XLD = more severe in males, can affect females Vit D levels can be normal PO4 wasting from renal tubules = low PO4 Treatment with PO4 & Calcitriol oral Vit D-dependent Rickets type 1 Presents 3-6 months Gene mutation in 1 a-hydroxylase with reduced activity Treatment with high doses of Vit D or 1-a-cholecalciferol Nutritional Rickets Common in darker skinned children Due to lack of light & dietary vit D, malabsorption, renal disease, CRF, Anticonvulsants.ALP elevated Low 25-hydroxycholecalciferol Normal 1,25-dihydroxycholecalciferol Normal PTH Liver disease à rickets Low 25-hydroxycholecalciferol & 1,25dihydroxycholecalciferol – due to poor fat absorption Hepatomegaly – RICKETS doesn’t cause hepatomegaly alone PO4 deficiency (Vit D resistant) – impaired PTH dependent reabsorption of PO4 in proximal renal tubule 2+ Ca deficiency – low absorption e.g. celiac Acidosis Sx – irritable, proximal muscle weakness, hypotonia, swollen wrists, lumbar lordosis Baby – craniotabes (thinning & softening of skull bones) 3-6 Months – enlargement of ends of ribs – rachitic ‘rosary’ 12-18 months – bowing in or out of long bones due to stress of walking Ix - low / normal Ca, low PO4 (except in renal osteodystrophy), high ALP, high PTH (except in hypophosphataemic rickets) Rx – treat underlying cause Osteopenia Bone mineral density > 2 SD below the mean (measure with DEXA) e.g. osteogenesis imperfecta, cushings, chronic inflammation rx: analgesia, physio, splinting, bisphosphonates and Ca + Vit D Osteogenesis imperfecta (types I-V) – AR inherited. Errors of procollagen à multiple # of fragile bones. AD or new mutations General features: blue sclerae, scoliosis, hypoplastic teeth, progressive deafness • Type I - Mild forms, normal height, some have blue sclera, reduced exercise tolerance but high pain tolerance (therefore some # not symptomatic & found later by x-ray & considered to be NAI), 50% will be deaf by 40 yrs • Type II - Extremely severe, often lethal. Small nose, micrognathia, in-utero fractures, beaded ribs, deformed long bones. Death from rib fragility, pulmonary hypoplasia or CNS malformation / haemorrhage • Type III – Severe – joint hyperlaxity, muscle weakness, chronic bone pain, skull deformity, blue sclera in most, limb shortening, in-utero fractures, vertigo, hypercalciuria, kyphoscoliosis à respiratory problems • Type IV – Undefined – a range of symptoms, can include all the above Rx – pamidronate infusions will reduce fracture risk. Dietician input to ensure sufficient Ca & Vit D, prophylactic nailing Osteopetrosis (aka - marble bone disease) Decreased osteoclasts à reduces bone breakdown à hardening & excess formation Despite increased osteoid = more brittle à # Due to narrowing of marrow spaces à anaemia à extra medullary haematopoesis à splenomegaly Overgrowth of skull (including formina) à cranial nerve palsies AR inheritance – severe, bone marrow failure à early death AD inheritance – less severe, bone #s, facial paralysis, osteomyelitis Scurvy Vit C deficiency- prevents normal collagen formation à intradermal & subperiosteal haemorrhage, haemarthrosis Weakness, fever, rapid drop Hb, petechial rash, peripheral oedema, bleeding gums, marrow shows ineffective haematopoesis Gout Only if increased urate secondary to renal failure, malignancy etc Lesch-Nyman = X-lined uric acid metabolism problem à CNS probs & gout in late teens Amyloid Plaques have protein fibrillary structure Can occur in: Familial Mediterranean syndrome Chronic inflammation Familial amyloidosis Multiple myeloma Alzheimers ] 2 most common in children ]