Rheumatology Flashcards

Question

SLE and pregnancy

Answer 1

Characteristics Fertility is not affected. Pregnancy may cause flares in disease activity. ↑ Risk of preterm birth, hypertensive complications (preeclampsia), intrauterine growth restriction, fetal AV block, and miscarriage Risk assessment [26] Cardiac, lung, and kidney screening Maternal antibodies: anti-Ro/SSA and anti-La/SSB Anticardiolipin antibodies and lupus anticoagulant (see antiphospholipid syndrome) Management Pregnancy planning and counseling Prednisolone , azathioprine; cyclosporin, tacrolimus , and hydroxychloroquine are considered safer drug options during preconception, pregnancy, and breastfeeding. Some immunosuppressive medications used to treat SLE (e.g. mycophenolate and cyclophosphamide) have severe teratogenic and other adverse fetal effects. Low-dose aspirin is recommended in all pregnant women from 12 weeks gestation Neonatal lupus syndrome Associated with the transfer of maternal antibodies (anti-Ro/SSA and anti-La/SSB) Symptoms: Periorbital or diffuse rash (often presents in the first weeks after birth) Cytopenia Hepatitis, elevated liver enzymes First- to third-degree congenital AV block

Answer 2

Osteoarthritis (OA) is a disabling joint disease characterized by a noninflammatory degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. It mainly affects the weight-bearing and high-use joints, such as the hip, knee, hands, and vertebrae. Despite the widespread view that OA is a condition caused exclusively by degenerative “wear and tear” of the joints, newer research indicates a significant heterogeneity of causation, including pre-existing peculiarities of joint anatomy, genetics, local inflammation, mechanical forces, and biochemical processes that are affected by proinflammatory mediators and proteases. Major risk factors include advanced age, obesity, previous injuries, and asymmetrically stressed joints. In early-stage osteoarthritis, patients may complain of reduced range of motion, joint-stiffness, and pain that is aggravated with heavy use. As the disease advances, nagging pain may also occur during the night or at rest. Diagnosis is predominantly based on clinical and radiological findings. Classic radiographic features of OA do not necessarily correlate with clinical symptoms and appearance. If lifestyle changes (moderate exercise, weight loss) and physical therapy fail to improve symptoms, nonsteroidal anti-inflammatory drugs (NSAIDs) in particular, are used for the management of active osteoarthritis. If medical interventions fail to improve the patient's quality of life, surgical procedures such as joint replacement may become necessary.

Answer 3

epidemiology: Most common joint disorder in the USA, affecting more than 20 million adults Incidence: increases with age Sex: ♀ > ♂, especially in patients older than 50 years Incidence rates in specific joints: knee > hip > hand Aetiology: Modifiable risk factors: Obesity, excessive joint loading or overuse. Non-modifiable risk factors: Age >55 years Familial history History of joint injury or trauma Anatomic factors causing asymmetrical joint stress Hemophillic hemarthroses and deposition diseases that stiffen cartilage Gender. ``` Classification: Idiopathic OA No identifiable, underlying cause Genetic factors of causation have been implicated, but not definitively proven. Secondary OA Hemochromatosis Wilson disease Ehlers-Danlos syndrome Diabetes Avascular necrosis Congenital disorders of joints Alkaptonuria Joint trauma ``` Pathophysiology: Joint damage/stress → cartilage damage → decreased proteoglycans levels → cartilage becomes friable and inelastic and starts to degrade → loss of joint space and bony surface → subchondral bone becomes thickened and sclerotic. Clinical features Early clinical findings Pain on exertion, which is relieved with rest Pain in both complete flexion and extension Crepitus on joint movement Joint stiffness and restricted range of motion Radiating or referred pain (e.g., coxarthrosis may lead to knee pain) Late clinical findings Constant pain (including at night) Morning joint stiffness usually lasting < 30 minutes More severely restricted range of motion Subtypes and variants Heberden's nodes: Pain and nodular thickening on the dorsal sides of the distal interphalangeal joints (DIP), ♀ > ♂ Bouchard's nodes: Pain and nodular thickening on the dorsal sides of the proximal interphalangeal joints (PIP), ♀ > ♂. Hallux rigidus: Arthrosis of the first metatarsophalangeal joint (between the first metatarsal and the first proximal phalanx), characterized by hypertrophy of the sesamoid bones. Osteoarthritis of the hip and knee In contrast to osteoarthritis, rheumatoid arthritis does not affect the DIP joints. ``` Investigations: Osteoarthritis is usually diagnosed on the basis of clinical and radiographic evidence of joint degeneration. Radiological signs of osteoarthritis Irregular joint space narrowing Subchondral sclerosis Osteophytes (also: bone spurs) Subchondral cysts The patient's history and clinical diagnosis are essential for the assessment and treatment of osteoarthritis! Radiographic signs often do not correlate with the patient's perception and clinical findings! ``` ddx: DDx of inflammatory arthritis (put on document as well) Osteoarthritis Rheumatoid arthritis Psoriatic arthritis Gout Pseudogout Other differential diagnoses: Autoimmune-related arthritis (e.g., sarcoidosis, SLE, rheumatic fever, mixed connective tissue disease, polymyalgia rheumatica) Arthritis associated with Inflammatory bowel disease Vasculitides Hemochromatosis Viral arthritis (e.g., parvovirus B19, hepatitis viruses) Lyme arthritis Reactive arthritis (post-urethritis, post-enteritis) Fibromyalgia treatment General Weight loss Regular exercise Shoe inserts (e.g., buffer insoles) in, e.g., valgus deformity of the knee Targeted muscle growth, physiotherapy, and medical training therapy Topical and heat therapy Pharmacotherapy Peripheral analgesics Acetaminophen NSAIDs: e.g., ibuprofen In combination with PPIs in patients with gastrointestinal risk (e.g., together with glucocorticoids) Opioid analgesics: e.g., tramadol Interventional therapy In severe courses: intraarticular glucocorticoid injections (not a long-term treatment!) Surgical therapy: if conservative and interventional measures fail Endoprosthesis (joint replacement) In case of failure of endoprosthesis or in select OA subtypes (e.g., Heberden's OA): arthrodesis (operative ankylosis) Pharmacotherapy should be used as acute and symptomatic therapy only; long-term NSAID therapy should be avoided due to its many side effects! Complications Untreated and/or severe cases can result in permanent damage to the joints with stiffening and deformity. Complications in the upper limbs: rheumatoid hand deformities (see “Clinical findings” above) Complications in the lower limbs Baker cyst due to inflammatory joint effusion Foot impairment: pes plano‑valgus Other complications [14] See "Subtypes and variants" above. Muscle weakness Lung disease: pleural and parenchymal lung diseases Cardiovascular disease: increased risk of pericarditis, coronary artery disease, heart failure, atrial fibrillation, and stroke Vasculitis involving the kidneys and skin Amyloid A (AA) amyloidosis Septic arthritis Osteopenia, osteoporosis, and bone fractures Sjögren syndrome (secondary form). ``` Prognosis Factors associated with poor prognosis Prolonged disease progression without initiation of treatment Late onset (> 60 years of age) Sex: ♀ Smoking Social factors (e.g., low socioeconomic status, low level of education) Laboratory tests associated with worsened prognosis if abnormally elevated CRP ESR ACPA RF titer ```

Answer 4

Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease that mainly affects patients above the age of 50 years and occurs twice as often in women than in men. Patients typically present with new-onset pain in their shoulders, hips or neck, morning stiffness, and systemic symptoms (e.g., fatigue, malaise, B symptoms, and depressed mood). In addition to clinical presentation, the diagnosis is made based on laboratory studies, which usually show a highly elevated erythrocyte sedimentation rate (ESR), while creatine kinase and autoantibodies are negative. Bursitis and serositis in the joints of the shoulder and pelvic girdle on ultrasound may also help to confirm the diagnosis. The most important step in the management of PMR is to administer a low dose of oral glucocorticoids and taper them slowly until full remission is achieved. Patients with polymyalgia rheumatica should be routinely monitored for symptoms of giant cell arteritis because this type of vasculitis commonly develops during the course of disease. epidemiology: Sex: ♀ > ♂ (2–3:1) Peak incidence: 70–79 years; rarely seen in patients < 50 years More common among individuals of northern European decent Most common inflammatory rheumatic disease in the elderly (second most common overall) Women of advanced age are particularly prone to the disease! Aetiology Unknown; possible contributing factors are: Genetic predisposition (e.g., human leukocyte antigen HLA-DR4) Association with giant cell arteritis: 10–20% of patients with polymyalgia rheumatica also have GCA ``` Clinical features Systemic symptoms Constitutional symptoms: fever, weight loss, night sweats Fatigue and malaise Depressed mood Symptoms of anemia Musculoskeletal symptoms: new onset, symmetric pain Shoulder and pelvic girdle, neck Worse at night Morning stiffness (> 45 min) Subjective weakness ∼ 10–20% of patients with polymyalgia rheumatica also develop typical symptoms of giant cell arteritis. ``` Diagnostics ↑↑ ESR, specifically > 50 mm/h ↑ CRP Leukocytosis Normochromic anemia Normal creatine kinase, negative rheumatoid factors and no autoantibodies Bursitis on ultrasound of affected joints DDx: Giant cell arteritis Both diseases often coexist and share common findings (e.g., elevated ESR, B symptoms) May develop during the course of PMR (patients should be routinely evaluated for symptoms of GCA) Rheumatoid arthritis: positive rheumatoid factor and/or anti-CCP antibodies Polymyositis and dermatomyositis: ↑↑ serum creatine kinase (normal in PMR) Fibromyalgia: normal laboratory values The differential diagnoses listed here are not exhaustive.Giant cell arteritis Both diseases often coexist and share common findings (e.g., elevated ESR, B symptoms) May develop during the course of PMR (patients should be routinely evaluated for symptoms of GCA) Rheumatoid arthritis: positive rheumatoid factor and/or anti-CCP antibodies Polymyositis and dermatomyositis: ↑↑ serum creatine kinase (normal in PMR) Fibromyalgia: normal laboratory values The differential diagnoses listed here are not exhaustive. Treatment Low-dose of oral glucocorticoids (alternative: IM glucocorticoids) If symptoms improve (usually within 2–4 weeks): slowly taper and eventually stop glucocorticoids No improvement after 2 weeks or relapse: increase dose

Answer 5

Giant cell arteritis (GCA) is a type of autoimmune vasculitis that causes chronic inflammation of large and medium-sized arteries, in particular the carotid arteries, its major branches, and the aorta. It is most common in white women over the age of 50, and approximately 50% of patients also have polymyalgia rheumatica. Patients usually present with constitutional symptoms (e.g., fever, weight loss, night sweats, fatigue, and malaise), new-onset headache, a tender, hardened temporal artery, jaw claudication, or amaurosis fugax. Laboratory tests typically show signs of inflammation (e.g., elevated erythrocyte sedimentation rate and CRP), and temporal artery biopsy should be performed to confirm the diagnosis. The classic histopathological findings are mononuclear infiltration of the vessel wall and formation of giant cells. If GCA is suspected, prompt administration of glucocorticoids is essential to reduce the risk of permanent vision loss and cerebral ischemia. Epidemiology Sex: ♀ > ♂ Peak incidence: 70–79 years; rarely seen in patients < 50 years Most common among individuals of northern European descent Women of advanced age are particularly prone to the disease! Aetiology: Unknown; possible contributing factors include: Genetic predisposition (e.g., human leukocyte antigen HLA-DR4) Viral infections (e.g., parvovirus B19) Association with polymyalgia rheumatica (PMR): 40–50% of patients with giant cell arteritis also have PMR. Pathophysiology Giant cell arteritis is thought to be due to a cell-mediated immune response to endothelial injury. However, the initiating factors are not fully understood. Inflammation Activation of dendritic cells in the adventitia of blood vessel walls → Dendritic cells recruit Th1 cells, CD8+ T cells, and monocytes. Monocytes differentiate to macrophages and giant cells, which produce cytokines (e.g., IL-6, TNF-α) that augment the inflammatory response. Local vascular damage: macrophages produce metalloproteinases → destruction of vessel wall structures (e.g., internal elastic lamina) Concentric intimal hyperplasia: macrophages and giant cells produce PDGF and VEGF → stimulate intimal proliferation → reduced blood flow and ischemia Clinical features: Constitutional symptoms Fever, weight loss, night sweats Symptoms of anemia: fatigue and malaise Symptoms of arterial inflammation: extracranial branches of the common carotid, internal carotid, and external carotid arteries (the temporal artery is the most commonly affected vessel) New-onset headache (can be pulse-synchronous, throbbing, dull); typically located over the temples Hardened and tender temporal artery Jaw claudication: jaw pain when chewing Vision loss Scintillating scotoma Amaurosis fugax or permanent loss of vision Diplopia Symptoms of polymyalgia rheumatica (if both diseases are present) Diagnostics: ACR criteria (3 of the 5 criteria are required) Age at disease onset ≥ 50 years Headaches Abnormalities of the temporal artery Elevated ESR (≥ 50 mm/h; see “Laboratory tests” below) Histopathological abnormalities in the temporal artery (see “Temporal artery biopsy” below) Laboratory tests ↑↑ ESR, specifically > 50 mm/h (However, a normal ESR does not rule out giant cell arteritis!)→ can lead to Rouleaux formation of RBCs ↑ CRP Mild thrombocytosis Normochromic anemia No autoantibodies Temporal artery biopsy (gold standard): mandatory in all patients pathology: Panarteritis of the large and medium-sized arteries Proliferation of the intima (and subsequent stenosis of the artery) Fragmentation of the internal elastic lamina Predominantly mononuclear infiltration of the vessel wall with formation of giant cells ``` ddx: Polymyalgia rheumatica Giant cell arteritis and polymyalgia rheumatica (PR) often occur simultaneously and share common features (e.g., elevated ESR, constitutional symptoms). PR causes shoulder girdle and pelvic stiffness and pain rather than ocular or cerebral findings. Other vasculitides Takayasu arteritis Polyarteritis nodosa Granulomatosis with polyangiitis Systemic lupus erythematosus Rheumatoid arthritis Other causes of monocular vision loss, e.g.: Carotid artery disease Thromboembolism Retinal vein occlusion ``` Treatment: Ischemic organ damage (e.g., impaired vision): high dose of IV glucocorticoids or oral glucocorticoids Uncomplicated disease: medium dose of oral glucocorticoids After symptoms have resolved (usually after 2–4 weeks), slowly taper glucocorticoids to the lowest dose that is needed to control symptoms (The mean duration of treatment is 1–2 years). Low-dose aspirin to prevent ischemic complications Tocilizumab (antagonizes IL-6 receptor) may be used to reduce the required dose of steroids. Immediate administration of high-dose glucocorticoids is crucial to prevent permanent vision loss in patients with giant cell arteritis! complications Permanent vision loss: ∼ 20–30% if giant cell arteritis is left untreated Cerebral ischemia (e.g., transient ischemic attack and stroke): < 2% of cases Aortic aneurysm and/or dissection: ∼ 10–20% of patients

Answer 6

Osteoporosis is a skeletal condition in which the loss of bone mineral density leads to decreased bone strength and an increased susceptibility to fractures. The disease typically affects postmenopausal women and the elderly, as an abrupt decrease in estrogen and age-related processes play a key role in the development of osteoporosis. Further risk factors include inactivity, smoking, and alcohol consumption. Osteoporosis usually remains asymptomatic until the first occurence of fragility fractures (following minor trauma), particularly of the vertebrae. After repeated vertebral fractures, patients may also develop thoracic hyperkyphosis and lose height. Osteoporosis is diagnosed through a bone density test (dual-energy X-ray absorptiometry), while fractures are usually confirmed through conventional x-ray. Management of osteoporosis includes prophylactic measures and medical therapy. The prophylaxis consists mainly of adequate intake of calcium and vitamin D and regular physical activity with strengthening exercises. Both help to maintain or even increase bone mass and improve balance, thereby reducing the risk of falling. Medical therapy is indicated in cases of severely reduced bone density or osteoporotic fractures. The most commonly used drugs are bisphosphonates, which inhibit bone resorption and can significantly decrease the risk of fractures. There are several other possible medical therapies (e.g., teriparatide, raloxifene), which may be indicated in special cases (e.g., severe osteoporosis, breast cancer prophylaxis required) or if patients have contraindications to bisphosphonates.

Answer 7

D: Osteoporosis: insufficient bone strength with increased susceptibility to fractures Osteopenia: decreased bone strength but less severe than osteoporosis ``` Risk factors Cigarette smoking Family history of osteoporosis Malabsorption, malnutrition (e.g., a vegan diet low in calcium and vitamin D) Low body weight ``` ``` Ddx: Osteomalacia Hyperparathyroidism Metastases Multiple myeloma Intraosseous hemangioma ``` Epidemiology: Sex: ♀ > ♂ (∼ 4:1) Age of onset: 50–70 years Demographics: higher incidence in individuals of Asian, Hispanic and northern European ancestry than in black populations Aetiology Primary osteoporosis (most common form) Type I (postmenopausal osteoporosis): postmenopausal women Estrogen stimulates osteoblasts and inhibits osteoclasts. The decreased estrogen levels following menopause lead to increased bone resorption. Type II (senile osteoporosis): gradual loss of bone mass as patients age (especially > 70 years) Secondary osteoporosis Drug-induced/iatrogenic: especially after systemic long-term therapy with corticosteroids (e.g., in patients with autoimmune disease) Other: Long-term therapy with anticonvulsants, L-thyroxine, anticoagulants,proton-pump inhibitors, aromatase inhibitors Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, renal disease Multiple myeloma Immobilization Alcohol abuse Clinical features: Mostly asymptomatic Pathological fractures: spontaneous fracture following mild physical exertion or minor trauma (e.g., lifting something, bending over, or sneezing/coughing) Localizations: vertebral (most common) > femoral neck > distal radius (Colles) fracture (Colles fracture), fractures of the long bones (e.g., humerus) Vertebral compression (crush) fractures are commonly asymptomatic, but may cause acute back pain and possible point tenderness without neurological symptoms Long-term findings after repeated vertebral compression fractures → Decreased height (loss of 2–3 cm with each fracture) → Thoracic hyperkyphosis → stooped posture with a “dowager's hump” Investigations DXA (dual-energy X-ray absorptiometry) Calculates bone mineral density (BMD) in g/cm2 Indications General recommendation for women ≥ 65 years and men ≥ 70 years In younger individuals if additional risk factors are present (e.g., prolonged glucocorticoid use, low BMI (< 21 kg/m2) or weight < 127 lb, alcohol use, smoker, amenorrhea) Results: T-score Osteoporosis: T-score ≤ -2.5 SD Osteopenia: T-score of -1 to -2.5 SD Plain radiography If osteoporosis is diagnosed: radiographic assessment of the whole skeletal system is recommended, particularly if a fracture is already suspected or height loss has occurred Increased radiolucency is detectable in cortical bones once 30–50% of bone mineral has been lost Osteoporosis can be diagnosed if vertebral compression fractures are present Commonly an incidental finding because such fractures are typically asymptomatic Clinical chemistry: usually normal (see Laboratory evaluation of bone disease), but some markers may be used for assessing risk of fracture Urine: ↑ cross-links (e.g., deoxypyridinoline), markers of bone turnover Blood tests Primary osteoporosis: Alkaline phosphatase possibly elevated Other parameters normal (e.g., serum calcium, phosphate) Secondary osteoporosis: abnormal results depending on underlying disease (e.g., hypercalcemia in hyperparathyroidism) Pathology: Thin, disconnected trabecular structures Attenuated, pitted cortical bone Increased osteoclast number and activity Osteoporosis is diagnosed if T-score ≤ -2.5 SD and/or a fragility fracture is present. Management Lifestyle measures Diet Avoid alcohol and nicotine Sufficient intake of calcium and vitamin D Physical activity with strength and balance training Avoid or minimize glucocorticoids Medical therapy Indication History of fragility fractures T-scores ≤ -2.5 T-score between -1 and -2.5 with severely increased risk of fracture Drugs 1st-line treatment: bisphosphonates (alendronate, risedronate); inhibit osteoclasts and therefore bone resorption Alternative treatment options: in the case of contraindications/unresponsiveness to bisphosphonates or certain risk factors Teriparatide (parathyroid hormone analog): alternative for severe osteoporosis (T-score ≤ -3.5) or for patients with contraindications to bisphosphonates Raloxifene (selective estrogen receptor modulator, SERM) for patients with contraindications to bisphosphonates or those who also require breast cancer prophylaxis (but increases the risk of thromboembolism) Denosumab (monoclonal antibody against RANKL) : for patients with impaired renal function, or no success with bisphosphonates Consider hormonal therapy Estrogens: for women with intolerance to 1st- or 2nd-line treatment options or with persistent menopausal symptoms Usually in combination with progestin Contraindications: breast cancer, coronary heart disease, deep vein thrombosis Testosterone: for men with hypogonadism Bisphosphonates should be taken in the morning and evening at least 30 minutes before meals to prevent bisphosphonates from forming complexes with calcium. To prevent esophagitis, they should also be taken with plenty of water and an upright position should be maintained for at least 30 minutes following intake!

Answer 8

Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by joint pain, swelling, and synovial destruction. RA predominantly affects middle-aged women. The condition can also cause various extra-articular manifestations such as rheumatoid nodules and pulmonary fibrosis. Diagnosis is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically used for diagnosis. Early intervention with disease-modifying antirheumatic drugs (DMARDs) plays a decisive role in successful treatment. RA is not curable, but early effective treatment may help offset severe complications (e.g., permanent damage to the affected joints).

Answer 9

Epidemiology: Prevalence: ∼ 1% in Caucasians; lower in African and Chinese population [1] Sex: ♀ > ♂ (3:1) Peak incidence: 30–50 years Aetiology: Chronic inflammatory autoimmune disorder of unknown etiology Hypotheses suggest the etiology is multifactorial, with the following factors playing a role: Genetic disposition: RA appears to be associated with specific HLA types (HLA-DR4, HLA-DR1). Environmental triggers (e.g., infection, tobacco) Hormonal factors Pathophysiology: Initially, non-specific inflammation affects the synovial tissue, which is later amplified by activation of T cells (autoimmune response). With time, it may lead to inflammatory joint effusion and synovial hypertrophy, as well as progressive destruction and deterioration of cartilage and bone. Synovial lining hyperplasia Pannus formation along the synovial tissue → produce proteinases → destroy cartilage extracellular matrix Patients with positive rheumatoid factor (RF) are more likely to develop extra-articular manifestations of rheumatoid arthritis. [7] ``` Clinical features Polyarthralgia Symmetrical pain and swelling of affected joints (also at rest). Frequently affected joints [10] Metacarpophalangeal joints (MCPJs) Proximal interphalangeal joints (PIPJs) Wrist joints Knee joints Usually not involved: DIP joints, first CMC joint, and the axial skeleton (except for the cervical spine, see RA of the cervical spine) Morning stiffness (often > 60 min) that usually improves with activity [11] Joint deformities "Rheumatoid hand" is characteristic, and can include the following deformities: Deepening of the interosseous spaces of the dorsum of hand Swan neck deformity: PIP hyperextension and DIP flexion Boutonniere deformity: PIP flexion and DIP hyperextension. Hitchhiker thumb deformity (Z deformity of the thumb): hyperextension of the interphalangeal joint with fixed flexion of the MCP joint Ulnar deviation of the fingers Hammer toe Atlanto-axial subluxation DIP joints are not typically affected in RA! ``` Extra-articular manifestations Constitutional symptoms: low-grade fever, myalgia, malaise, fatigue, weight loss, night sweats Skin: rheumatoid nodules Non-tender, firm, subcutaneous swellings (2 mm–5 cm) Commonly occur in areas exposed to higher pressure e.g., extensor side of the forearm, bony prominences Lungs Fibrosis, pneumoconiosis (Caplan syndrome) Rheumatoid pulmonary nodules Pleuritis, pleural effusions Eye: keratoconjunctivitis sicca, scleritis, and episcleritis Endocrine and exocrine glands: secondary Sjögren syndrome Hematological Anemia of chronic disease Neutropenia Splenomegaly (Felty syndrome) Other musculoskeletal Tenosynovitis and bursitis Carpal tunnel syndrome (entrapment neuropathy) Typical nocturnal paresthesia of volar hand and fingers I–III Atrophy of thenar muscles → difficulty making a fist; inability to oppose the thumb Tarsal tunnel syndrome Heart: pericarditis and myocarditis; higher risk of myocardial infarction, stroke, and CHF Vascular: peripheral vasculitis manifesting as livedo reticularis, Raynaud phenomenon, purpura, necrosing fingertips or peripheral neuropathy. Investigations: The diagnosis of RA is based on diagnostic criteria that include laboratory testing. Imaging may support the diagnosis, but radiological joint findings are no longer included in the criteria, as they often become evident only in late stages of disease. Laboratory tests Non‑specific parameters ↑ Inflammatory markers: CRP, ESR correlate with inflammatory activity. ↑ Ferritin as an acute phase protein Possibly leukocytosis, thrombocytosis Anemia of chronic disease Serology (specific parameters) ACPA (e.g., anti-CCP ) Specificity > 90% Rheumatoid factor (RF) IgM autoantibodies against the Fc region of IgG Low specificity Antinuclear antibodies (ANA): elevated in 30% of cases Synovial fluid analysis Synovial fluid is collected by joint aspiration. Findings Cloudy yellow appearance Sterile specimen with leukocytosis (WBC: 5,000–50,000/μL) ↑ Neutrophils, granulocytes, and ragocytes ↑ Proteins, ↓ viscosity Possibly rheumatoid factor. Imaging Conventional x-ray Dorso-palmar x-ray of both hands Radiological findings Early: soft tissue swelling, demineralization (juxta‑articular) Late: joint space narrowing, erosions of cartilage and bone, demineralization (generalized) Even if radiographic findings are normal, RA is still possible! MRI: (with or without contrast), especially if cervical spine involvement is suspected or in early stages Ultrasound: joint effusion, formation of pannus Further diagnostic measures: contrast-enhanced ultrasound, scintigraphy Before undergoing general anesthesia, airway and neck assessment is crucial in patients with rheumatoid arthritis. Atlanto-axial subluxation may be present, which increases the risk for spinal cord injury. Preoperative flexion-extension radiographs can help to evaluate the position of the cervical vertebra atlas (C1) with regard to the axis (C2). Pathology: Synovial pannus formation and bone invasion: proliferative granulation tissue with mononuclear inflammatory cells Angiogenesis Synovial lining hyperplasia with mononuclear cell infiltrate Perivascular inflammatory infiltrates Fibrin deposition on synovial surfaces Characteristic histology of rheumatoid nodules: central fibrinoid necrosis with histiocytes and surrounding epithelioid cells DDx: of inflammatory arthritis Treatment: General measures For acute episodes of inflammation: cryotherapy Physical and occupational therapy Physical activity Acute anti-inflammatory therapy Indication: acute attack Glucocorticoids: given until DMARD's onset of action or as long-term therapy for highly active RA. Systemic Intra-articular injections of PRN Prevention of osteoporosis: optimization of sufficient calcium and vitamin D intake NSAIDs and COX-2 inhibitors: symptomatic relief without improving prognosis PPIs are recommended because combining glucocorticoids with NSAIDs substantially increases the risk of GI ulcers. Long-term anti-inflammatory therapy with disease-modifying antirheumatic drugs (DMARDs) Induce immunosuppression, leading to potential remission of RA Reduce mortality and morbidity by up to 30% Slow progression of disease Preserve joint function Limit complications Slow onset of action (≥ 6 weeks), so symptomatic treatment with glucocorticoids and NSAIDs is often required Non-biologic agents Drug of choice: methotrexate (MTX) First-line treatment for moderate to severe RA Benefits: highly effective, relatively well-tolerated, low cost, possibly life-prolonging Gastrointestinal side effects , rash, hepatotoxicity (abnormal liver chemistry), interstitial pneumonitis and pulmonary fibrosis, bone marrow suppression , nephrotoxicity, increased risk of lymphoproliferative disorders, teratogenicity, alopecia [36] To minimize side effects, folic acid is recommended 24–48 hours after taking MTX. Do not give NSAIDs on the same day as MTX, as they can worsen the side effects of MTX by inhibiting its renal excretion . Alternative drugs: Leflunomide Hydroxychloroquine Sulfasalazine: for use in pregnancy Biologic therapy Indication: moderate or severe disease activity remaining after three months of DMARD therapy Should be combined with non-biologic DMARDs Tumor necrosis factor (TNF) α inhibitors: e.g., adalimumab, infliximab, etanercept See contraindications to anti-TNF-α treatment. Others: rituximab (anti-CD20) and anakinra (interleukin-1 receptor antagonist, particularly for Still disease) Early administration of DMARDs is crucial for a better outcome! Complications: Untreated and/or severe cases can result in permanent damage to the joints with stiffening and deformity. Complications in the upper limbs: rheumatoid hand deformities (see “Clinical findings” above) Complications in the lower limbs Baker cyst due to inflammatory joint effusion Foot impairment: pes plano‑valgus Other complications [14] See "Subtypes and variants" above. Muscle weakness Lung disease: pleural and parenchymal lung diseases Cardiovascular disease: increased risk of pericarditis, coronary artery disease, heart failure, atrial fibrillation, and stroke Vasculitis involving the kidneys and skin Amyloid A (AA) amyloidosis Septic arthritis Osteopenia, osteoporosis, and bone fractures Sjögren syndrome (secondary form). ``` Prognosis Factors associated with poor prognosis Prolonged disease progression without initiation of treatment Late onset (> 60 years of age) Sex: ♀ Smoking Social factors (e.g., low socioeconomic status, low level of education) Laboratory tests associated with worsened prognosis if abnormally elevated CRP ESR ACPA RF titer ```

Answer 10

Definition: inflammation of joints (primarily on hands, feet, spine) that may occur with psoriasis Epidemiology: 5–30% of psoriasis patients affected Clinical features Psoriasis and psoriatic arthritis may occur independently or together There are several types of psoriatic arthritis: Oligoarthritis (most common, accounting for 70% of cases): typically with involvement of both the distal and proximal interphalangeal joints Spinal involvement (up to 40% of cases) Other rheumatological features Enthesitis Tenosynovitis Dactylitis: inflammation and swelling of fingers or toes (“sausage digit”) Arthritis mutilans: destruction of the IP joints and resorption of the phalanges; causes the soft tissue of the fingers to collapse (“telescoping fingers” or “opera glass hand”) Diagnosis There is no specific test for diagnosing psoriatic arthritis The ClASsification Criteria for Psoriatic ARthritis (CASPAR) is helpful for diagnosing psoriatic arthritis (≥ 3 out of the 5 following points required). Evidence of psoriasis Psoriatic nail dystrophy Negative rheumatoid factor (RF) Dactylitis Radiologic signs Imaging studies: joint destruction, ankylosis Fingers: pencil-in-cup deformity Spine: syndesmophytes, and in particular asymmetric paravertebral ossification Treatment Mild disease: NSAIDs Moderate to severe disease: disease-modifying antirheumatic drugs (DMARDs) Physical therapy If first-degree relatives of patients with psoriasis have joint problems, psoriatic arthritis should be considered! If first-degree relatives of patients with psoriasis have joint problems, psoriatic arthritis should be considered!

Answer 11

Ankylosing spondylitis (spondyloarthritis), a type of seronegative spondyloarthropathy, is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell's sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease. The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumor necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life. Epidemiology Sex: ♂ > ♀ (3:1) Age: 15–40 years Lifetime prevalence in the US: ∼0.5% Aetiology Genetic predisposition: 90–95% of patients are HLA-B27 positive Clinical features Articular symptoms Most common presenting symptoms: back and neck pain Gradual onset of dull pain that progresses slowly Morning stiffness that improves with activity Pain is independent of positioning, also appears at night Tenderness over the sacroiliac joints Limited mobility of the spine (especially reduced forward lumbar flexion) Inflammatory enthesitis (e.g., of the Achilles tendon, iliac crests, tibial tuberosities): painful on palpation Dactylitis Arthritis outside the spine (hip, shoulder, knee joint) Extra-articular manifestations Most common: acute, unilateral anterior uveitis (∼ 25% of cases) Fatigue, weakness, fever, weight loss Restrictive pulmonary disease due to decreased mobility of the spine and thorax Gastrointestinal symptoms: associated with chronic inflammatory bowel disease (∼ 5–10% of cases, see also: ulcerative colitis or Crohn disease) Prostatitis Rare Cardiac: aortic root inflammation and subsequent aortic valve insufficiency, atrioventricular blocks Kidney: IgA-nephropathy Investigations Diagnostic approach Physical examination, patient history, and pelvic x-ray: If results are conclusive, no additional testing is required! If inconclusive → HLA-B27 testing If still inconclusive → pelvic MRI Clinical tests Chest expansion measurement: to monitor disease severity Method: measure chest circumference in full expiration and inspiration Pathological difference: < 2 cm Physiological difference: > 5 cm Spine mobility tests Schober test : Mark two points, S1 and another point 10 cm above → patient touches toes (without bending the knees) → distance between the two points increases by ≥ 4 cm → physiological test result; a smaller increase in distance between these two points is pathological Examination of the hip [3] Mennell sign: tenderness to percussion and pain on displacement of the sacroiliac joints FABER test: FABER (Flexion, ABduction, and External Rotation) provokes pain in the ipsilateral hip The degree of decrease in chest expansion is an important determinant of disease severity. Schober test Laboratory findings ↑ CRP and ESR Auto-antibodies (e.g., rheumatoid factor, antinuclear antibodies) are negative HLA-B27 positive in 90–95% of cases However, < 5% of HLA-B27 positive individuals have ankylosing spondylitis. Imaging X-ray Helps confirm a diagnosis and evaluate the severity of disease Changes are generally more evident in later disease. The changes usually occur symmetrically. Pelvis (best initial test): to examine the sacroiliac joints Signs of sacroiliitis, including ankylosis (fusion of the articular surfaces) Spine Loss of lordosis with increasing abnormal straightening of the spine Sclerosis of the vertebral ligamentous apparatus Syndesmophytes resulting in a so-called 'bamboo spine' in anteroposterior radiograph in the later stages (see the table in “Differential diagnosis” below) Signs of spondyloarthritis, including ankylosis of intervertebral joints [4] Thorax: ankylosis of costosternal and costovertebral joints Mild courses may only exhibit inflammatory changes in the sacroiliac joints on x-ray after a number of years. MRI More sensitive than CT scan for detecting sacroiliitis [5] Best method for early detection. Ddx: Mechanical low back pain Fibromyalgia Disc prolapse Vertebral osteomyelitis Other spondyloarthritides (e.g., reactive arthritis, psoriasis arthritis, arthritis associated with inflammatory bowel disease) Diffuse idiopathic skeletal hyperostosis (DISH; also called Forestier's disease or hyperostotic spondylosis) Definition: degenerative disease of the vertebral column (especially the thoracic and lumbar spine), which is characterized by calcification and ossification of spinal ligaments and entheses Epidemiology Not related to HLA-B27 [8] Mostly affects men Common in patients with diabetes Clinical presentation Limited mobility Mild or even no pain at all Diagnosis X-ray of the spine Formation of osteophytes (see table below) No sacroiliitis Treatment: symptomatic Osteophytes of the spine Syndesmophytes grow vertically, as opposed to osteophytes, which grow horizontally! Syndesmophytes: -Ossification or calcification of the annulus fibrosus or a spinal ligament -symmetrical, vertical growth, directly from vertebral body to vertebral body. Full manifestation: bamboo spine Inflammatory spine disease (ankylosing spondylitis). Osteophytes: lipping of vertebral bodies Horizontal growth Degenerative spine diseases (e.g diffuse idiopathic skeletal hyperostosis). Treatment Physical therapy Consistent and rigorous physical therapy Independent exercises Medical therapy First choice: NSAIDs (e.g., indomethacin) Additional options Tumor necrosis factor-α inhibitors (e.g., etanercept, adalimumab) [12] In case of peripheral arthritis: DMARDs (especially sulfasalazine) In severe cases: temporary, intra-articular glucocorticoids Surgery: in severe cases to improve quality of life Indications Severe deformity of the spinal column Instability of the spine Neurologic deficits Procedures Osteotomy Joint replacement Spinal fusion Physical therapy is the most important treatment modality! Complications: Complete fusion of the spine → severely limited mobility Increased risk of osteoporosis → pathological fractures and possibly spinal cord injury Restricted chest expansion and spine mobility → breathing difficulties

Rheumatology Flashcards

(35 cards)