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Rheumatology Board Review Presentation - 2 Vikas Majithia Game-Plan Stimulate your mind and think with me Highlight the topics Go over “educational objectives” These are potential questions/test pertinent areas Participate If you want write, Use the handout from today otherwise just listen SUBJ ECTIVE COMPLAINTS OF WEAKN ESS Excl ude: Anemia Card iopulmonary disease Chronic infections Malignancy Depression Fibro myalgia Malingering Deconditioning OBJ ECTIVE MUS CLE WEAKNESS AS YMMETRIC Regional neuro logical disorders Cerebrovascular disorders Spinal cord and spinal root disorders Demyelinating disease Co mpression neuropathy Mononeuropathy/mononeuritis multip lex Disuse atrophy Myasthenia gravis SYMMETRIC PROXIMAL Inflammatory myopathy Metabolic myopathy Endocrine myopathy Glucocorticoid myopathy Mitochondrial myopathy Drug-induced myopathy HIV-related myopathy Duchene’s muscular dystrophy Myasthenia gravis SPECIFIC PATTERN Muscular dystrophy Hereditary neuropathies Myasthenia gravis DISTAL Peripheral polyneuropathy Motor neuron disease Myasthenia gravis Inflammatory Myopathy: • Symmetric pro ximal muscle weakness • Elevated plasma muscle en zy mes • Myopathic changes on electromyography • Characteristic muscle biopsy abnormalities and the absence of histopathologic signs of other myopathies • Typical rash of dermato myositis Management includes complete laboratory profile, EM G, Biopsy. Work-up for underlying malignancy. Start prednisone at .5 mg/kg- 1 mg/kg initially. Needs appointment in rheumatology in 4-6 weeks or earlier. Dermatomyositis-Polymyositis Classification Criteria Five criteria for DM and PM were proposed in 1975 Symmetric proximal muscle weakness Elevated plasma muscle enzymes Myopathic changes on electromyography Characteristic muscle biopsy abnormalities and the absence of histopathologic signs of other myopathies Typical rash of dermatomyositis Dermatomyositis-Polymyositis Other clinical features 1. fever and weight loss, 2. A nonerosive inflammatory polyarthritis, 3. Raynaud's phenomenon 4. Cardiopulmonary abnormalities also may occur. 5. Congestive heart failure due to myocarditis 6. Interstitial lung disease MYOSITIS SPECIFIC ANTIBODIES: Anti T Rna Synthetases : Anti Jo-1: associated with ILD Anti Mi-2 (Dm) Anti Pm-SCL Anti SRP: associated with cardiac disease Heliotrope Rash Gottron’s sign/papules ©Copyright Science Press Internet Services DIFFERENCES BETWEEN DM AND PM Clinically, DM is associated with certain skin manifestations. Ocular muscles are more frequently involved in DM. DM Has a higher incidence of malignancy, although various cancers (GI, Lung, Ovary) can be associated with both DM and PM. Pathogenetically, DM is associated with immune complex deposition in the vessels, whereas PM appears to reflect direct T cell-mediated muscle injury. TREATMENT Corticosteroids 1 mg/kg are medications of choice IV pulse steroids may be needed Usually needed for a long duration: months to years. Immunosuppressive therapies: Azathioprine (Imuran) Methotrexate Combination of MTX and imuran IV cyclophosphamide IVIG Biologics- TNF blockers, Rituximab Inflammatory Myopathy Questions asked 1. 2. 3. 4. 5. 6. 7. Patient scenario: middle aged or elderly female. Male age above 50. Patient presents with weakness, hand and eyelid rash. Work-up should include? Likely diagnosis? Same patient is at risk for what? What tests to do? Additional tests in female patient? Patient with myositis presents with cough, SOB. What test? Antibody? Diagnosis? Patient with myositis responded to steroids and MTX now weak again, CPK is 650. Diagnosis? Management? 65 year-old-male comes with weakness, CPK 600, abnormal EMG. Treated with prednisone, MTX for 5-6 months but no response. Diagnosis? Appropriate test? Treatment? Myositis patient with left hip pain and abnormal exam. What test? Likely diagnosis? Monoarthritis Monoarthralgia Exclude Periarticular Disease Tendonitis, Bursitis, Bone lesion, Myofascial Pain, Sprain/Overuse, soft tissue infection, peri-articular GC infection Monarticular Arthritis/ Arthalgia Always consider Aspiration of joint for diagnosis Cell count, Crystals, Gram stain, Culture Infection Gonococcus Staphylococcus Streptococcus Diagnostic features: True joint Inflammation with pain, swelling, erythema, Leukocytosis and fever, Synovial fluid cell count >50,000, Positive gram stain and culture Crystalline disease Gout/pseudo gout True inflammatory changes in joint with urate or CPPD crystals on synovial fluid examination; cell count of 2000-50,000; Cystic erosions (gout) or chondorcalcinosis (pseudgout) on X-ray Osteoarthritis/trauma Absence of inflammatory changes and <30 minutes AM stiffness with the presence of pain, crepitus, mild swelling, osteophytes; X-ray changes of joint narrowing, osteophytes formation, sclerosis; Joint fluid aspirate either bloody or cell count<2000; If diabetic, consider neuropathic joint Seronegative spondyloarthropathy Inflammatory changes of joint (particularly knee or ankle); Synovial fluid cell count of 2000- 50,000; involvement of eyes (conjunctivitis or uveitis) or back/sacroiliac joints with prolonged (>1 hour AM stiffness) Early onset inflammatory arthritis RA or SLE Inflammatory joint changes with other etiologies excluded; with prolonged (>1 hour AM stiffness); with positive RF or ANA Septic Arthritis Synovial Fluid Analysis Normal Inflammatory Septic Hemorrha gic Crystal Induced Clear/Yellow Transparent Yellow/ White Translucent/ opaque Yellow/White Opaque Red Opaque Yellow/ White, Translucent /opaque <2K 2K-50K >50K N/a 10K-50K +/- Gm stain, +/Culture -ve Gm stain, Cx. -ve Gm stain, Cx. + Crystals -ve Gm stain -ve Gm stain & & Culture (Cx) Culture Disseminated GC Skin pustules in DGC Infectious arthritis Questions asked 1. Patient scenario: Male, Acute symptoms (sub-acute female in DGI) 2. Elderly male presents to the ER with acute R knee pain/swelling: Next test, Results abnormal- What to do? 3. 20-40 year old F with migratory arthritis: Knee-ankle-wrist, Tap shows 15,000 wbc. Has a rash. Diagnosis? 4. Travel to Connecticut, rash, fatigue, myalgia? History? Diagnosis? Treatment? 5. Same patient (did not get treatment)1 year later has CN palsy/knee arthritis. What to do? Polyarthritis/ Polyarthralgia Determine by History and Physical if inflammatory (Prolonged AM stiffness, erythema, swelling, warmth, pain) Evaluation dictated by history and physical may include CBC, urinalysis, liver and kidney function, RF, ANA, ANCA, ESR, TSH, CPK, HBA1C, CXR and regional/back/SI joint X-rays Non- Inflammatory AM stiffness < 1 hour No joint erythema, swelling and Normal ESR Negative RF or ANA Implies a differential diagnosis of Myofascial pain Fibromyalgia Osteoarthritis Endocrinopathy Pain syndrome Does not clearly fit into either category, Consider: Seronegative RA Seronegative spondyloarthropathy Inflammatory AM stiffness > 1 hour Joint erythema, swelling, or pain And Elevated ESR (must exclude other inflammatory diseases such as infection or cancer) Or Positive RF Positive ANA Implies a differential diagnosis of: Rheumatoid arthritis Connective tissue disease (lupus, PSS, PM/DM, Sjogren’s) Viral infection Seronegative spondyloarthropathy Sarcoidosis SPONDYLOARTHROPATHIES Ankylosing spondylitis Reiter's syndrome or reactive arthritis Arthropathy of inflammatory bowel disease Psoriatic arthritis Undifferentiated spondyloarthropathies Juvenile chronic arthritis and juvenileonset ankylosing spondylitis CLINICAL CHARACTERISTICS OF SPONDYLOARTHROPATHIES Tendency to cause sacroiliitis Tendency to cause spondylitis Association with enthesopathy (enthesitis) Typical pattern of peripheral arthritis: usually lower limb, asymmetric, tenosynovitis (sausage digits) Absence of rheumatoid factor (RF) Absence of subcutaneous nodules and other extraarticular features of rheumatoid arthritis (RA) Overlapping extra-articular features characteristic of the group (e.g., anterior uveitis) Significant familial aggregation and association with HLA-B27 Sausage Digits Management Physical modalities NSAIDS DMARDs New treatments- TNF alpha blockers. Ankylosing Spondylitis Inflammatory back pain HLA B-27 associated Symmetrical Sacroilitis Spondylitis: erosion, squaring of the vertebrae Uveitis; symmetrical Atypical presentations: female, older age Occiput to wall test Schobere’s test Enthesopathy. Reiter’s Syndrome Inflammatory oligoarticular arthritis in the setting of previous or intercurrent nongonococcal urethritis and/or conjunctivitis is characteristic of patients with Reiter’s syndrome. It is important to recognize that the majority of patients with this disorder present with just one or two features of the triad. Clinical triad of urethritis, conjunctivitis, and inflammatory arthritis. Mucocutaneous manifestations of Reiter’s syndrome: Circinate Balanitis and keratoderma Enthesopathy. Keratoderma Blenorrhagica Spondyloarthropathy/Infectious arthritis Questions asked 1. 2. 3. 4. 5. 6. Patient scenario: Male, sub-acute symptoms Patient with back pain worse in AM and better with activity. What test? What eye manifestation (different in RA)? Differentiate from non-inflammatory back pain? AS patient come with widened pulse pressure, heart murmur. What test? Diagnosis? AS patient comes with weakness in legs, BB incontinence. Diagnosis? Treatment? AS patient with pain/numbness affecting all 4 Ext UE>LE? Recently rear-ended? Next test? Diagnosis? AS patient with SOB? Diagnosis? Spondyloarthropathy/Infectious arthritis Questions asked 7. Patient with R knee arthritis, h/o STD. Diagnosis? Eye manifestation? Associated Disease? 8. Patient with painful DIP, swollen 2nd toe. Exam has nail pitting, What else to look for? Diagnosis? 9. Japanese patient with recurrent oral/genital ulcers, arthritis. Diagnosis? Treatment? 10. Cruise ship (trip to Mexico etc) had diarrhoea, Now with 1-2 joint arthritis +/- sausage toe. Likely diagnosis? Associated organisms? 11. AS patient with back pain not responding to NSAIDs and SSZ. Treatment? THE VASCULITIDES CLASSIFICATION SIZE OF THE VESSELS INVOLVED ORGAN SYSTEMS INVOLVED CLASSIFICATION Large vessel: GCA and temporal arteritis, Takayasu’s arteritis, Primary angitis of CNS Medium size vessels: PAN, Kawasaki disease, Churg strauss syndrome, Wegener’s granulomatosis Small vessels: CS syndrome, Wegener’s granulomatosis, HSP, Microscopic angitis, Mixed cryoglobulinemia, Hypersensitivity vasculitis/leukocytoclastic vasculitis, Vasculitis associated with rheumatic diseases- RA,SLE Misc. : Behcet’s disease, Relapsing polychondritis, Lymphomatoid granulomatosis CLINICAL MANIFESTATIONS NON SPECIFIC: Fatigue and weakness Fever, skin rash Arthralgias and/or arthritis abdominal pain hypertension neurological dysfunction/neuritis. SPECIFIC: PERTAINING TO THE ORANS INVOLVED Pulmonary nodules Sinus /nasal inflammation Gastrointestinal inflammation with its presenting symptoms Glomerulonephritis/renal insufficiency with an active sediment. Hypersensitivity /leukocytoclastic vasculitis Age >16 a possible offending agent in temporal relation to the symptoms Palpable purpura Maculopapular rash Biopsy of a skin lesion showing neutrophils around an arteriole or venule ANY OF THE VASCULITIDES WHICH CAN INVOLVE SMALL VESSELS CAN PRESENT AS PALPABLE PURPURA & HAVE A PATHOLOGY OF LEUKOCYTOCLASTIC VASCULITIS THERAPY Hypersensitivity vasculitis – Discontinuing the offending agent may be adequate NSAIDS,Antihistamines. Colchicine, dapsone Corticosteroids as needed Occasionally cytotoxic agents are required. Systemic vasculitis : Corticosteroids are almost always needed. Cytotoxic agents have to be used in a number of instances. Rituximab in ANCA associated Vasculitis (AAV) Classification Criteria Wegner’s Granulomatosis Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge) Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities Abnormal urinary sediment (microscopic hematuria with or without red cell casts) Granulomatous inflammation on biopsy of an artery or perivascular area C-ANCA (anti proteinase-3) is now an important diagnostic test. Up to 90% sensitive in active systemic disease. Tissue biopsy can be diagnostic--A nasopharyngeal lesion, Renal biopsy, Lung biopsy Saddle nose Nodules POLYARTERITIS NODOSA ACR Classification criteria: 3/10 + are 82% sensitive, 84% specific • • • • • • • • • • Otherwise unexplained weight loss greater than 4 kg Livedo reticularis Testicular pain or tenderness Myalgias (excluding shoulder and hip girdle), weakness of muscles, tenderness of leg muscles Mononeuropathy (Mononeuritis Multiplex) or polyneuropathy New onset diastolic blood pressure greater than 90 mmHg Elevated levels of serum blood urea nitrogen or creatinine Evidence of hepatitis B virus infection Characteristic arteriographic abnormalities A biopsy of small or medium-sized artery containing PMN’s. Renal angiogram Giant Cell (Temporal) Arteritis & Polymyalgia Rheumatica PMR is classically characterized by aching and morning stiffness in the shoulder, hip girdles, neck and torso in patients over the age of 50. The symptoms are usually symmetric and associated with a high ESR, but asymmetric pain and normal ESR can occur. GCA (temporal) arteritis is a chronic vasculitis of large and medium size vessels which commonly occurs among individuals over 50 years of age. Polymyalgia rheumatica occurs in about 50 percent of patients with GCA, while approximately 15 percent of patients with PMR as the primary diagnosis develop GCA Symptoms/signs • NON SPECIFIC: fatigue, weakness, fever, arthralgias. • SPECIFIC: new headache(60-70 %) jaw claudication (30-40%) Permanent partial or complete loss of vision in one or both eyes(15-20%) arm claudication (10 %) Tender or thickened temporal arteries. Bruits in cranial and upper extremity vessels • Characteristic laboratory abnormality is a high ESR upto 100mm/h. normal values may occasionally be seen. CRITERIA FOR GCA Age greater than or equal to 50 years at time of disease onset Localized headache of new onset Tenderness or decreased pulse of the temporal artery Erythrocyte sedimentation rate greater than 50 mm/h (Westergren) Biopsy which includes an artery, and reveals a necrotizing arteritis with a predominance of mononuclear cells or a granulomatous process with multinucleated giant cells TREATMENT Corticosteroids are the mainstay of treatment Prednisone is started in at 10-20 mg for PMR and titrated to a response in clinical and laboratory markers. For GCA prednisone is started at a higher dose of 0.5 to 1 mg/kg. IV steroids may be needed for acute visual changes. Subsequently Slow taper is recommended. Usually treatment is continued for 1- 2 years after remission. Cytotoxic medications and methotrexate can be used and may be required both during acute and chronic phases. Classification Criteria for Relapsing Polychondritis • • • • • • Recurrent chondritis of both auricles Nonerosive inflammatory polyarthritis Chondritis of nasal cartilage Inflammation of ocular structures, including conjunctivitis, keratitis, scleritis/episcleritis and/or uveitis Chondritis of the respiratory tract involving laryngeal and/or tracheal cartilages Cochlear and/or vestibular damage manifest by neurosensory hearing loss, tinnitus, and/or vertigo The Vasculitides Questions asked 1. 2. 3. 4. 5. 6. 7. Elderly (>50) patient presents with fever, stiffness? Next test? Treatment? Same patient has headache, visual loss. Next test? Shortcoming of the test? Treatment? Young Asian/Hispanic patient with pain, weakness in left arm. Finding on exam? Next test? Diagnosis? Male patient with abdominal pain, weight loss, arthritis, leg ulcers, purpuric rash. Next test? Diagnosis? Associated findings? Same patient also has history of IV drug abuse. underlying disease? What results on ANCA testing? Same patient with foot drop. Diagnosis? Next test? 40-50 year old male patient with abdominal pain, arthritis, leg ulcers, purpuric rash. Next test? Diagnosis? Associated findings? The Vasculitides Questions asked 8. 9. 10. 11. 12. 13. 14. 15. 16. Male patient with SOB, cough, weight loss, active urinary sediment, + p-ANCA. Next test? Diagnosis? Treatment? Patient with sinusitis, nasal ulcer. Next test? Diagnosis? Treatment? Same patient with hemoptysis, cough, renal insufficiency? Next test? Diagnosis? Treatment? Patient with h/o asthma, rhinitis, now has cough, purpuric rash. chest x-ray: infiltrates. Next test? Diagnosis? Treatment? Purpuric rash, URI, hematuria. Diagnosis? Treatment? Urticarial rash, hematuria- active urinary sediment- Dx & Tx? Recreational drug assoc pseudovasculitis- clinically vasculitis, -ve imaging & bx. Serology- ANCAs may be +. Culprit drugs? Cutting agents? Tests? Patient started on HCTZ, now has a rash: palpable purpura. Diagnosis? Management? Patient of Mediterranean descent with recurrent abdominal pain, fever, arthritis. + family history. Diagnosis? Treatment? Complication? Osteoporosis: Diagnosis and Evaluation Central DXA (Dual Energy X-ray Absorptiometry) remains the state-ofthe-art diagnostic standard Bone density is the most important predictor of fracture risk What is a T-score? What is a Z-score? The BMD results are expressed as standard deviations from a comparison to the referent mean. A T-SCORE is the number of standard deviations the bone mineral density measurement is above or below the YOUNG-NORMAL MEAN bone mineral density. A Z-SCORE is the number of standard deviations the measurement is above or below the AGEMATCHED MEAN bone mineral density. World Health Organization Interpretation of Bone Density Patient’s T-Score -0.5 T Classification Normal -1.0 T -1.5 T -2.0 T Osteopenia -2.5 T Osteoporosis Severe Osteoporosis (with fragility fractures) National Osteoporosis Foundation Who should be evaluated for OP. • Bone density test vs Fracture risk assessment? • Women: o Age > 65 without risk factors o Age > 50 with risk factors1 • Men o Age > 70 o Earlier – if there are risk factors*- osteoporotic fracture, hypogonadism, malignancy etc. 1. Risk factors for osteoporotic fracture include: low body weight; history of fracture; Caucasian; cigarette smoking; estrogen deficiency, early menopause; low calcium intake; alcoholism; recurrent falls; and inadequate physical activity. * Not well-defined Fracture Risk Assessment Score- FRAX • FRAX- Tool to assess fracture risk (Developed by WHO) • Decision making alogrithm for assessing the risk of fracture in an individual based on clinical information and using that to make therapeutic decisions. • Can add BMD in the calculation • Gives a 10-year risk • A 10 year risk of overall fracture > 20% or hip fracture > 3% is felt to be significant. National Osteoporosis Foundation Who should be considered for treatment of OP. • Complicated answer • Women: o Age > 40 with low BMD (T-score <-2.5 i.e. OP) or high FRAX (T-score>1&<2.5 i.e. osteopenia) o Age < 40- individualize (risk factors, fracture, steroid use) • Men o low BMD (T-score <-2.5) or high FRAX o Younger patient, ?Age - individualize (risk factors, fracture, steroid use) Traditional Nonpharmacological Management for Prevention and Treatment Calcium (1200 – 1500 mg/day in divided doses) Vitamin D 400-800 IU/day* Weight-bearing exercise Fall-prevention techniques *800 IU/day for patients over age 65 Fracture Prevention: Role of Drug Therapy Anti-resorptive therapies: Hormone replacement therapy (HRT) Raloxifene Bisphosphonates Alendronate Risedronate Ibandronate Pamidronate Zolendronate Calcitonin RANK Ligand inhibitor- Denosumab (Prolia) Bone formative: PTH (Forteo) Osteoarthritis Primarily a disorder of cartilage associated with cartilage destruction and secondary bone changes Most Common rheumatic disorder Common cause of joint pain especially in elderly Joint Pain: weight bearing joints, worse with activity & better with rest AM stiffness is minimal Typically involves DIP and PIP Can have secondary synovitis (inflammation) Common cause of back pain: remember SPINAL STENOSIS and its features Typically normal lab studies X-rays: joint space narrowing and osteophyte formation Osteoarthritis Management •Acetaminophen •NSAIDs: Any NSAID works fine •Weight reduction and physical therapy •Local therapy •Intra-articular steroids •Intra-articular viscous supplementation ( Hyalgan, Synvisc etc) only in knee OA •Narcotics Role of joint replacement Surgery: •Treat patient not radiograph •Symptoms of Rest pain and night pain are indications for surgery •Functional impairment is also indication for surgery •Adequate medical work-up due to risk factors Back Pain Mechanical Back Pain Minimal AM stiffness Intermittent Improved with rest Decreased ROM in all directions Inflammatory Back pain Prolonged AM stiffness Persistent Improved with activity Decrease in Flexion/extension of spine: Schobere’s test Remember symptoms and neurological signs of nerve impingement syndromes at various levels Remember back pain (typically at night time) in elderly could be sign of malignancy Remember back pain in elderly/immunosuppresed could be sign of chronic infection typically TB Fibromyalgia Clinical Syndrome not a disease Typically middle aged white females No objective sign of joint inflammation Associated with myofascial pain, fatigue, stiffness, lethargy Alterations in normal sleep pattern Associated with psychiatric syndromes, IBS, migraine, premenstrual syndrome No diagnostic test: must rule out a serious underlying disorder Tender points on examination ( 11 out of 18) Management includes: counseling, improving sleep hygiene, graded exercise, SSRIs, Muscle relaxants, Ultram, treatment of psychiatry disorders Osteoarthritis, OP, Fibromyalgia and Back pain Questions asked 1. Patient with severe, persistent knee/hip pain, night pain. Treatment? 2. X-Ray findings, Treatment algorithm for OA 3. 70-year-old female with back pain, night time worsening, point tenderness. Likely Diagnosis? 4. 30-year-old with back pain radiating to leg. No neurological deficit. Diagnosis? Treatment? 5. 45 year old with left sided back pain, radiation to foot, can not dorsi-flex big toe. What level is impingement? What reflex to look for? 6. 35 year old female with fatigue, aching, poor sleep, ANA 1:40. Likely diagnosis? Treatment? 7. 50 year old with history of radius fracture? What to workup for? Test of choice? 8. Male with OP? testing? 9. Secondary causes of OP? 10. Comparative efficacy of various agents, SE and C/I 11. Fracture risk reduction of various agents Other Board Pertinent Disorders Pain, swelling of extremity after trauma. Area cool to touch, edematous, Hyperalgesia? Diagnosis? Test of choice? Shoulder Injury and now pain in wrists/hands with above findings. Treatment? Lyme disease- Arthritis (2nd stage), associated fibromyalgia. No ABX treatment of arthritis if treated in past Pain hip: remember back/spine origin, tender outside (lateral side) of hips-diagnosis? Pain knee: Normal exam,, Look for hip abnormality. Pain knee: normal exam- ilio-tibial band syndrome. Medial side of tibia. Diagnosis? Other Board Pertinent Disorders Sarcoidosis: EN, Lofgren’s syndrome, others Obese or diabetic patient with pain/burning pain ant thigh. Mild Sensory loss. Normal EMG. Diagnosis? 60 year old, smoker with pain in ankles, hands. Tender above ankle, clubbing, radiographs periosteitis. Diagnosis? Corticosteroid toxicities including associated myopathy, AVN and osteoporosis Carpal Tunnel Syndrome & association with hypothyroidism. Buerger’s disease/ Thromboangiitis obliterans Non-atherosclerotic, segmental, inflammatory disease that most commonly affects the small and medium sized arteries, veins, and nerves of the extremities Normal ESR & CRP Cellular/Inflammatory thrombus Normal: auto-antibodies/other serologic tests Cork screw blood vessels Stop smoking Osteomalacia, Vitamin D deficiency Usually, the cause of osteomalacia is a deficiency in vitamin D There are other causes: Low phosphate Normal 25-OH vitamin D levels: 30 ng/ml Replace with 50, 000 units once or twice a week for 3-6 months DISH Calcification and ossification along the anterolateral aspect of at least four contiguous vertebral bodies Preservation of intervertebral disc height Lack of findings of AS Paget’s Disease (osteitis deformans) Focal skeletal disorder characterized by an accelerated rate of bone turnover. CLINICAL MANIFESTATIONS Pain Skeletal deformities and fractures Bone tumors (remember osteosarcoma) Neurologic complications (Hearing loss, CN Palsies) Cardiac complications: Heart failure, Aortic stenosis, Conduction abnormalities Calcium and phosphate metabolism, Elevated Alkaline phosphatase. Treatment: Bisphosphonates Erythema Nodosum Causes Idiopathic Sarcoidosis IBD TB Fungal URI: Viral/Bacterial OCs CTD Treatment NSAIDs Potassium Iodide GCs Treat underlying disease GOOD LUCK (REMEMBER DINNER AT CHAR IS GOING TO AWAIT YOU)