Rheumatology PDF

RA 04 August 2024 6:48 PM Definition ○ RA is a chronic systemic autoimmune disorder causing a symmetrical polyarthritis. Incidence ○ It has female-to-male predominance of 3:1. ○ Prevalence ↑ with age, with a typical age at onset of 20 to 40 years. Etiology...

RA 04 August 2024 6:48 PM Definition ○ RA is a chronic systemic autoimmune disorder causing a symmetrical polyarthritis. Incidence ○ It has female-to-male predominance of 3:1. ○ Prevalence ↑ with age, with a typical age at onset of 20 to 40 years. Etiology ○ Gender ▪ Women before the menopause are affected three times more often than men, with an equal sex incidence thereafter suggesting an aetiological role for sex hormones. ○ Familial ▪ There is an increased incidence in those with a family history of RA. ○ Genetic factors ▪ Human leucocyte antigen (HLA)-DR4 and HLA-DRB1 0404/0401 confer susceptibility to RA and are associated with development of more severe erosive disease. Protein tyrosine phosphatase N22 (PTPN22), STAT4 and PADI-4 have also been identified as susceptibility genes.* ○ Smoking ▪ is an environmental risk factor for seropositive RA. ○ The triggering antigen in RA is not known Pathophysiology ○ RA is characterized by synovitis (inflammation of the synovial lining of joints, tendon sheaths or bursae) with thickening of the synovial lining and infiltration by inflammatory cells. ○ Generation of new synovial blood vessels is induced by angiogenic cytokines, and activated endothelial cells produce adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), which expedite extravasation of leucocytes into the synovium. ○ The synovium proliferates and grows out over the surface of cartilage, producing a tumour-like mass called ‘pannus’. ○ Pannus destroys the articular cartilage and subchondral bone, producing bony erosions. Clinical features ○ Articular manifestations ▪ Pattern of involvement □ Symmetric inflammatory polyarthritis □ Typically involves >3 joints; predominately affecting these seven sites: MCP, PIP, wrist, elbow, knee, ankle, and MTP □ TIP: The hands are involved in almost all patients with RA; however, RA spares the DIP joints. ▪ Symptoms of affected joint □ Morning pain and/or stiffness for >60 minutes for at least 6 weeks. □ Symptoms improve with joint use and worsens with prolonged inactivity (Gelling phenomenon). □ The presence of erythema, warmth, and/or swelling in the joint □ Characteristic hand deformities include ulnar deviation of the fingers at the MCPs, swan neck deformities, and boutonniere deformities. ▪ Spinal affection □ RA commonly affects the cervical spine—be aware of the risk of C1-C2 (“atlanto- axial”) subluxation in patients with chronic RA and obtain cervical spine x-ray prior to tracheal intubation to assess for this. C1-C2 subluxation may be asymptomatic or produce occipital headaches or cervical myelopathy. Extra-articular findings of RA Rheumatology Page 1  ○ Extra-articular findings of RA Peri-articular Bursitis, tenosynovitis, muscle wasting and subcutaneous nodules (rheumatoid nodules) Cardiac Pericarditis, myocarditis, atherosclerosis Raynaud’s syndrome Pulmonary Pleural effusion (low glucose and high LDH), interstitial lung disease, pulmonary nodules, Caplan syndrome (Rheumatoid pneumoconiosis) Obliterative bronchiolitis Eyes Episcleritis, scleritis, keratitis, uveitis, Sjögren syndrome, Scleromalacia perforans (perforation of the eye) Renal Amyloid renal disease, Analgesic nephropathy Nerve Mononeuritis multiplex, cervical myelopathy, carpal tunnel syndrome Cord compression Polyneuropathy, predominantly sensory Skin Rheumatoid nodules (usually extensor surface) Nodules occur in 25% of cases Usually over pressure points at the elbow, the finger joints and Achilles tendon. Nodules may also occur in the pleura, pericardium and lung. Blood Anemia of chronic disease, thrombocytosis, Felty syndrome (RA, neutropenia, and splenomegaly) Lymphadenopathy Other Vasculitis (Leg ulcers, Nail fold infarcts, Gangrene of fingers and toes), AA amyloidosis (2° amyloidosis) ○ Forms of presentations ▪ Early □ Joint effusions and wasting of muscles around the affected joints are early features. ▪ Aggressive □ Aggressive RA is probable with: □ High titers of RF, +ve anti-CCP, +ve HLA.-DR4 antigen □ Insidious onset, □ Constitutional symptoms, □ Early erosive disease on x-ray, □ Early appearance of rheumatoid nodules. ▪ Late ▪ Less common presentations are □ Explosive: sudden onset of widespread arthritis □ Palindromic relapsing and remitting monoarthritis of different large joints □ With a systemic illness with few joint symptoms initially. ○ Constitutional symptoms ▪ Fever, Fatigue, Weight loss Differential diagnosis ○ In a young woman with bilateral symmetric arthritis of the hands and wrists, the differential is RA, SLE, and viral infection. If the symptoms abate within 6 weeks, RA is less likely, and viral syndromes (such as Rheumatology Page 2  ○ If the symptoms abate within 6 weeks, RA is less likely, and viral syndromes (such as parvovirus, EBV, HBV, HCV, and rubella) are more likely. Plain x-rays may not distinguish early RA from SLE, as radiographic erosions take time to develop. ○ RA must be distinguished from symmetrical seronegative spondyloarthropathies; severe RA can mimic a form of psori- atic arthritis known as ‘arthritis mutilans Diagnosis ○ Diagnostic criteria A +ve serology is now required for diagnosis. CRITERION DESCRIPTIO POINTS N Joint involvement (swollen, tender, or erosions seen on x- 1 large joint ray) 2-10 large joints 1-3 small joints 4-10 small joints ○ Radiology ▪ Classic radiographic findings: ▪ Periarticular osteopenia, ▪ joint space narrowing, ▪ juxtaarticular erosions, ▪ erosions of the ulnar styloids ▪ Early radiographic RA findings can often be seen first in the feet, particularly fifth MTP joint. ○ Lab ▪ RF □ RF are antibodies against the fragment crystallizable region (Fc region) portion of IgG. □ “Rheumatoid factor” (RF) is poorly named, because it is not specific to RA. □ Diseases associated with ⊕ RF include: other rheumatologic diseases (SLE, Sjögren), viral infections (HCV, EBV, parvovirus, influenza), chronic bacterial infections and normal aging. □ Only 50% of patients with RA have ⊕ RF at onset, and up to 20%— particularly men—never become RF ⊕. □ Fluctuation in RF titer does not correlate with disease activity, but extremely high titers correlate with aggressive course. □ Most extra-articular manifestations of RA are observed in patients who are “seropositive” (meaning RF ⊕ and/or anti-CCP ⊕) and have long-standing erosive articular disease. ▪ Anti-CCP □ More specific (90%-95%) but less sensitive than RF antibody. □ Patients with ⊕ anti-CCP are at ↑ risk for radiographic progression of RA. □ Anti-CCP is more specific but less sensitive than RF for diagnosing RA. When used together, the two tests maximize the sensitivity and specificity of a diagnosis of RA. ▪ ESR and CRP are frequently ↑ but are neither sensitive nor specific. ▪ Anemia of chronic disease is common. ▪ Platelet count is normal or ↑ (vs. a low platelet count in SLE). ▪ Synovial fluid is sterile with a high neutrophil count in uncomplicated disease. Management ○ General guidlines ▪ Assess disease activity based on history, physical exam, and standardized Disease Activity Score: ▪ Low disease activity: Start with disease-modifying antirheumatic drug (DMARD) monotherapy. ▪ High disease activity: Combination DMARD therapy or anti-TNF therapy. ▪ Early use of DMARDs is key to minimizing damage and reducing disability. Rheumatology Page 3  ▪ Early use of DMARDs is key to minimizing damage and reducing disability. ▪ For patients with RA or SLE, prednisone and hydroxychloroquine are the preferred anti-inflammatory agents during pregnancy.(Remember the 3P’s: For Pregnancy, use Prednisone or Plaquenil). ○ Nonbiologic DMARDs ▪ Methotrexate □ Indications First-line DMARD □ Dosage Weekly □ Initial monitoring CXR, hepatitis serologic tests, CBC, LFTs, Cr □ Routine monitoring CBC, LFTs every 4-8 weeks □ Contraindications Renal disease, hepatic disease, EtOH abuse, pregnancy/trying to conceive □ Side effects Myelosuppression, hepatotoxicity, cirrhosis, teratogenicity (F and M), GI intolerance, stomatitis, alopecia, hypersensitivity pneumonitis, pulmonary fibrosis In a patient being treated with methotrexate for RA who presents with new-onset dyspnea and interstitial infiltrates on CXR, consider opportunistic infection and hypersensitivity pneumonitis from methotrexate and discontinue the drug. Folic acid reduces side effects but may also reduce efficacy. ▪ Sulfasalazine □ Indications First- or second- line DMARD □ Dosage Daily □ Initial monitoring CBC, G6PD (if suspected) □ Routine monitoring CBC, LFTs □ Contraindications G6PD deficiency (can cause hemolysis), sulfa allergy □ Side effects GI intolerance, transaminitis, neutropenia, thrombocytopenia ▪ Leflunomide □ Indications First- or second-line DMARD □ Dosage Daily, but t1/2 is >2 weeks □ Initial monitoring Hepatitis serologic tests, CBC, LFTs, Cr □ Routine monitoring CBC, LFTs, Cr □ Contraindications Pregnancy/trying to conceive, EtOH abuse, hepatic disease □ Side effects Myelosuppression, hepatotoxicity, rash, diarrhea, alopecia, tergatogenicity ▪ Hydroxychloroquine □ Indications First- or second- line DMARD □ Dosage Daily Rheumatology Page 4  Daily □ Routine monitoring Yearly eye exam □ Side effects Retinopathy, especially with renal dysfunction ○ Corticosteroids ▪ Indications □ First-line DMARD, but use lowest dose possible and wean off to prevent long-term complications ▪ Dosage □ Daily oral; joint injections are very helpful for symptoms ▪ Initial monitoring □ BP, glucose, metabolic panel, lipids ▪ Routine monitoring □ Bone densitometry (DEXA), glucose, lipids ▪ Contraindications □ Caution in osteoporosis,severe diabetes ▪ Side effects □ Glucose intolerance, hypertension, cataracts, osteoporosis, avascular necrosis ○ NSAIDs ▪ Effective in relieving the joint pain and stiffness of RA, but they do not slow disease progression. ▪ Slow-release preparations (e.g. slow-release diclofenac) taken at night may produce dramatic relief of symptoms on the following day. ▪ Paracetamol with or without codeine or dihydrocodeine can be added for additional pain relief. ○ Biologic DMARDs ▪ TNF-α inhibitors, □ Indications Second-line DMARDs/ biologics; usually added after 3-6 months if there is little or no response to other DMARDs □ Dosage Infliximab: Infusion q 6-8 weeks Adalimumab: SQ injection q 2 weeks Etanercept: SQ injection 1-2 per week Certolizumab: SQ injection 1-2 per month Golimumab: SQ injection 1 per month □ Initial monitoring PPD or IGRA, CXR, CBC, LFTs, hepatitis serology testing □ Routine monitoring CBC, LFTs □ Contraindications Malignancy; active or untreated latent TB □ Side effects With all agents: Immunosuppression with an ↑ incidence of opportunistic infections and malignancy; all can cause drug-induced lupus (⊕ anti-ds-DNA) Infliximab is associated with higher rates of infusion reactions and of neutralizing antibodies than other TNF inhibitors because it is a chimeric (mouse and human) antibody. ▪ Azathioprine □ Indications Used for severe/ refractory RA □ Dosage Daily □ Initial monitoring CBC, LFTs, Cr, low TPMT activity Rheumatology Page 5  CBC, LFTs, Cr, low TPMT activity □ Routine monitoring CBC with change in dose, LFTs □ Contraindications Not to be used concomitantly with allopurinol □ Side effects Myelosuppression, immunosuppression, hepatotoxicity, lymphoproliferative disorders ▪ Tocilizumab, □ Indications Used for severe RA, IL-6 receptor inhibitor □ Dosage Monthly □ Initial monitoring PPD or IGRA, CBC, chemistry, LFTs, hepatitis serology testing □ Routine monitoring CBC, chemistry, LFTs, lipids □ Contraindications ANC