Inflammatory connective tissue disorders Notes


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This Osmosis High-Yield Note provides an overview of Inflammatory connective tissue disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Inflammatory connective tissue disorders:

Systemic lupus erythematosus

CREST syndrome


Mixed connective tissue disease

Polymyalgia rheumatica

Raynaud phenomenon


Sjogren syndrome

NOTES NOTES INFLAMMATORY CONNECTIVE TISSUE DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Chronic autoimmune disorders characterized by inflammation; primarily affect connective tissue ▪ Production of autoantibodies → deposition of immune complexes → complement activation → tissue destruction ▪ Inflammatory cytokines stimulate fibroblasts → increased collagen deposition (fibrosis) ▪ Affects multiple organ systems ▫ Skin, heart, respiratory system, urinary, gastrointestinal (GI) tract CAUSES ▪ Genetic, environmental factors COMPLICATIONS ▪ Skin necrosis; renal, cardiac failure; pulmonary insufficiency; GI reflux/bleeding SIGNS & SYMPTOMS ▪ Constitutional symptoms ▫ Low grade fever, fatigue, weight loss ▪ Specific to disease, organ systems affected ▫ “Butterfly skin rash” specific to systemic lupus erythematosus (SLE) DIAGNOSIS DIAGNOSTIC IMAGING Barium swallow X-ray ▪ GI involvement LAB RESULTS ▪ Blood tests ▫ Hematologic abnormalities, increased inflammatory markers, complications (e.g. increased creatinine reflecting renal failure) ▪ Serological tests ▫ Antibodies, confirm diagnosis OTHER DIAGNOSTICS ▪ Physical examination (e.g. characteristic skin rashes) ▪ Pulmonary function tests ▫ Pulmonary involvement TREATMENT ▪ Usually symptomatic (e.g. analgesics) MEDICATIONS ▪ Steroids/other immunosuppressive agents ▫ Reduce inflammation OSMOSIS.ORG 639
CREST SYNDROME PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Form of limited systemic sclerosis ▪ Composed of five features; see mnemonic ▫ Calcinosis: deposition of calcium under skin ▫ Raynaud’s syndrome: episodic, dramatic constriction of arteries in hands ▫ Esophageal dysmotility: atrophied muscle in esophagus without significant inflammation/fibrosis ▫ Sclerodactyly: fibrosis of skin of digits ▫ Telangiectasia: dilation of small blood vessels ▪ Caused by chronic autoimmune inflammation triggered mainly by anticentromere antibodies (ACAs) ▪ More benign clinical course than other forms of sclerosis ▪ Calcific nodules under the skin ▪ White-blue-red transitions in skin color in response to triggers (e.g. low temperature, stress) ▪ Dysphagia (due to esophageal dysmotility) ▪ Sclerodactyly ▪ Telangiectasias (esp. hands, face) MNEMONIC: CREST Features of CREST syndrome Calcinosis Raynaud’s syndrome Esophageal dysmotility Sclerodactyly Telangiectasia COMPLICATIONS ▪ Ischemic ulcers, gangrene, predisposition to chronic skin infections (due to sclerosis, severe ischemia of skin) ▪ Upper GI bleeding (due to mucosal telangiectasias) Figure 112.1 Sclerodactyly in an individual with CREST syndrome. DIAGNOSIS LAB RESULTS ▪ Serum blood tests ▫ ↑ ANAs: sensitive for systemic sclerosis ▫ ↑ ACAs: highly specific (limited systemic sclerosis); confirm diagnosis OTHER DIAGNOSTICS ▪ Clinical history, physical examination TREATMENT MEDICATIONS ▪ Steroids ▪ If sclerosis progresses, stronger immunosuppressants (e.g. cyclosporine) 640 OSMOSIS.ORG
Chapter 112 Inflammatory Connective Tissue Disorders FIBROMYALGIA PATHOLOGY & CAUSES ▪ Chronic condition of central sensitization; hypersensitivity to pain, sleep disturbances ▫ ↓ serotonin (inhibits pain signals) ▫ ↑ substance P, ↑ nerve growth factor (involved in propagating pain signals) ▫ Predominance in individuals who are biologically female CAUSES ▪ Genetic factors ▪ Environmental factors (child abuse) ▪ Negative emotions (depression, anxiety, negative beliefs) can amplify pain SIGNS & SYMPTOMS ▪ Low threshold to pain ▪ Widespread muscle pain ▪ Extreme tenderness in various parts of body ▪ Sleep disturbances → fatigue, headache ▪ Difficulty concentrating, remembering things; AKA “fibro fog” DIAGNOSIS OTHER DIAGNOSTICS Diagnostic Criteria ▪ Pain in ≥ seven areas of body with symptom severity (SS) of ≥ 5 (of 12)/pain in ≥ five areas of body with SS of ≥ 9 (of 12) ▪ Final score between 0–12 ▪ Symptoms present ≥ three months ▪ Pain not due to another disorder Symptom severity (SS) measures ▪ Fatigue; waking unrefreshed; cognitive symptoms; somatic symptoms ▫ 0: no problem ▫ 1: slight/mild/intermittent ▫ 2: moderate/considerable/often present ▫ 3: severe, continuous, life disturbing TREATMENT MEDICATIONS ▪ If non-pharmacologic measures fail, drug therapy ▪ Antidepressants ▫ Inhibit pain by elevating levels of serotonin, norepinephrine ▫ Tricyclic antidepressants (TCAs): amitriptyline first line treatment ▫ Serotonin-norepinephrine reuptake inhibitors (SNRIs): milnacipran ▪ Anticonvulsants ▫ Slow nerve impulses, relieve sleep disturbances PSYCHOTHERAPY ▪ Cognitive behavioral therapy (CBT) ▫ Manage pain, change negative feelings OTHER INTERVENTIONS ▪ Physical therapy, relaxation techniques, sleep hygiene to reduce pain, fatigue OSMOSIS.ORG 641
MIXED CONNECTIVE TISSUE DISEASE (MCTD) PATHOLOGY & CAUSES DIAGNOSIS ▪ Overlap autoimmune syndrome; constellation of SLE, systemic sclerosis, polymyositis; may not occur simultaneously ▪ Can evolve into classic SLE/systemic sclerosis ▪ Confirmation requires characteristic clinical presentation COMPLICATIONS ▪ Pulmonary hypertension; interstitial lung disease; renal disease SIGNS & SYMPTOMS ▪ Arthralgias (due to polyarthritis) ▪ Myalgias (due to mild myositis) ▪ Swollen hands with puffy fingers (due to synovitis) ▪ Sclerodactyly ▪ Early development of Raynaud phenomenon ▪ Fatigue ▪ Low-grade fevers 642 OSMOSIS.ORG LAB RESULTS ▪ High serum levels of anti-U1 ribonucleoprotein (anti-U1-RNP) antibodies ▪ High ANAs, RF, anti dsDNA, anti Sm, anti Ro TREATMENT ▪ Depends on predominant autoimmune disease MEDICATIONS ▪ Corticosteroids ▫ Suppress immune system
Chapter 112 Inflammatory Connective Tissue Disorders POLYMYALGIA RHEUMATICA (PMR) PATHOLOGY & CAUSES ▪ Immune-mediated rheumatic condition affecting joints, sparing muscles ▪ Most commonly affects shoulder, hip joints ▪ Usually occurs in individuals who are biologically female > 50; mean age 70 ▪ Strongly associated with giant-cell arteritis, AKA temporal arteritis ▪ Can regress without treatment after 1–2 years/remain chronic CAUSES ▪ Genetic defects: specific allele of human leukocyte antigen (HLA)-DR4 ▪ Environmental factors: exposure to adenovirus/human parvovirus B19 SIGNS & SYMPTOMS ▪ Joint pain, stiffness (shoulder, hip joints) ▫ Often starts unilaterally, progresses to bilateral within few weeks ▫ More severe after prolonged inactivity (e.g. morning) ▫ Typically lasts > one hour ▫ Affects nearby nerves in muscle → muscle pain (referred pain) ▪ Constitutional symptoms ▫ Low grade fever (interleukins act as pyrogens) ▫ Fatigue ▫ Loss of appetite → weight loss ▪ If severe headache, jaw pain, vision problems ▫ Temporal arteritis DIAGNOSIS LAB RESULTS ▪ Increased serum inflammatory markers ▫ Erythrocyte sedimentation rate (ESR) ▫ C-reactive protein (CRP) ▪ Biopsy ▫ Inflammation in joints OTHER DIAGNOSTICS ▪ Physical examination ▫ Decreased passive range of motion of affected joints TREATMENT MEDICATIONS ▪ Low dose of corticosteroids ▫ Suppress immune response OSMOSIS.ORG 643
RAYNAUD'S DISEASE PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Vasospasm of skin arteries in response to triggers, resulting in skin color transitions ▪ Exposure to trigger → stimulation of sympathetic nerves in arteriole walls → vasospasm of arterioles → decrease in blood flow ▪ Usually affects hands, fingers, toes; can affect nose, ears, lips ▪ Common triggers ▫ Emotional stress; low temperatures; nicotine; caffeine; medications that affect sympathetic nervous system (e.g. pseudoephedrine) ▪ Vasospasm → changes in skin color of hands, fingers, toes ▫ White: ischemia ▫ Blue: hypoxia after prolonged ischemia ▫ Red: reactive hyperemia (vasospasm ends, oxygenated blood rushes into tissue) ▪ Raynaud phenomenon ▫ Affects hand fingers, toes symmetrically; severity remains constant ▪ Raynaud syndrome ▫ Asymmetrical; progressive severity ▪ Swelling, numbness, tingling, pain (due to reactive hyperemia) TYPES Primary: Raynaud phenomenon/disease ▪ Common in pregnant individuals, people who work in jobs involving vibration (e.g. jackhammer) Secondary: Raynaud syndrome ▪ Connective tissue disorders ▫ Systemic lupus erythematosus (SLE), scleroderma, mixed connective tissue disease ▪ Disorders affecting blood vessels ▫ Buerger’s disease, Takayasu’s arteritis, thromboangiitis obliterans ▪ Medications ▫ Beta blockers, nicotine COMPLICATIONS ▪ Ulceration, infarction, tissue necrosis, gangrene (if severe) DIAGNOSIS ▪ Based upon description of episodes DIAGNOSTIC IMAGING ▪ Nailfold capillary microscopy to examine finger capillaries ▫ Normal appearance: Raynaud phenomenon ▫ Damaged appearance: Raynaud syndrome TREATMENT MEDICATIONS ▪ Vasodilators (e.g. calcium channel blockers) SURGERY ▪ If severe, surgery to cut sympathetic nerve fibers supplying affected areas OTHER INTERVENTIONS ▪ Avoid triggers 644 OSMOSIS.ORG
Chapter 112 Inflammatory Connective Tissue Disorders Figure 112.2 A hand with pale fingers caused by Raynaud’s disease. SCLERODERMA PATHOLOGY & CAUSES ▪ AKA systemic sclerosis ▪ Chronic inflammatory autoimmune disease, can result in widespread damage to small blood vessels, excessive fibrosis ▫ T helper cells activated by unknown antigen → release cytokines → stimulate inflammatory cells, fibroblasts → chronic inflammation, excessive collagen deposition ▫ Mediators released by inflammatory cells → damage microvasculature → ischemic injuries, scarring ▪ Primarily affects skin, can involve visceral organs ▫ GI tract, kidneys, heart, muscles, lungs TYPES Limited (80%) ▪ Skin involvement limited to fingers, forearms, face ▪ Late visceral involvement ▪ Some individuals develop CREST syndrome ▫ Calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia ▪ Associated with anticentromere antibodies ▪ Relatively benign Diffuse (20%) ▪ Widespread skin involvement ▪ Early visceral involvement ▪ Rapid progression ▪ Associated with anti-DNA topoisomerase I antibodies ▪ Poor prognosis RISK FACTORS ▪ More common in individuals who are biologically female (3:1 ratio) ▪ Average age of onset: 35–50 ▪ Genetic factors ▪ Environmental factors (e.g. viruses, toxins, drugs) OSMOSIS.ORG 645
COMPLICATIONS ▪ Excessive skin fibrosis → painful ulcers, disfigurement, disability ▪ Severe internal organ involvement → renal, cardiac failure; pulmonary insufficiency; intestinal malabsorption SIGNS & SYMPTOMS ▪ Raynaud phenomenon ▫ Precedes other symptoms, present in almost all individuals ▪ Cutaneous changes of face, extremities ▫ Skin thickening, tightening, sclerosis (most common); edema, erythema (precede sclerosis) ▪ GI involvement ▫ Esophageal fibrosis → dysphagia, GI reflux ▫ Small intestine involvement → abdominal pain, obstructions, constipation, diarrhea, malabsorption syndrome (weight loss, anemia) ▪ Pulmonary involvement with interstitial fibrosis ▫ Right-sided cardiac dysfunction/ pulmonary hypertension ▪ Cardiac involvement ▫ Pericardial effusions, myocardial fibrosis → congestive heart failure, arrhythmias ▪ Renal involvement (diffuse disease) → fatal hypertensive crisis (rare) Figure 112.3 The finger of an individual with systemic sclerosis showing sclerosis, erythema and ulcer formation. DIAGNOSIS DIAGNOSTIC IMAGING ▪ Upper endoscopy ▫ Esophageal fibrosis/reflux esophagitis LAB RESULTS ▪ Serologic tests ▫ ↑ ANAs in almost all individuals with systemic sclerosis; low specificity ▫ ↑ ACAs highly specific (limited) ▫ Anti-topoisomerase I antibodies (antiScl-70) highly specific (diffuse) ▪ Complete blood count (CBC) ▫ Anemia due to malabsorption, increased serum creatinine due to renal dysfunction OTHER DIAGNOSTICS ▪ Clinical presentation ▫ Skin thickening, swollen fingers, Raynaud’s phenomenon, GI reflux ▪ Pulmonary function tests ▫ Restrictive ventilatory defect due to pulmonary interstitial fibrosis Figure 112.4 A rash on the back of an individual with a form of localised scleroderma known as morphea. 646 OSMOSIS.ORG
Chapter 112 Inflammatory Connective Tissue Disorders TREATMENT ▪ Depends on disease subset, severity of internal organ involvement MEDICATIONS ▪ Usually symptomatic ▫ Analgesics for musculoskeletal pain ▫ Proton pump inhibitors for gastroesophageal reflux ▫ Calcium channel blockers for Raynaud’s phenomenon ▫ Angiotensin converting enzyme (ACE) inhibitors for renal hypertensive crisis ▪ Immunosuppressive therapy initiation: diffuse skin/severe internal organ involvement SJOGREN'S SYNDROME (SS) PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Chronic autoimmune inflammatory disease; lymphocytic infiltration, destruction of exocrine glands of eyes, mouth ▪ Proposed mechanisms ▫ Immune reactions against antigens of viral infection of exocrine glands ▫ Autoimmune T cell reaction against unknown self antigen expressed in salivary, lacrimal glands ▪ Variety of extraglandular manifestations may occur ▪ Usually occurs in individuals who are biologically female, 50–60 years ▪ Dry eyes ▫ Irritation, itching, foreign body sensation, keratoconjunctivitis ▪ Oral dryness reflecting salivary hypofunction ▪ Salivary gland enlargement (parotid, submandibular, etc.) ▪ Extraglandular manifestations ▫ Musculoskeletal symptoms (arthralgias, arthritis); rashes; interstitial nephritis, vasculitis CAUSES ▪ Primary: sicca syndrome ▪ Secondary (to other autoimmune diseases): rheumatoid arthritis (most common) COMPLICATIONS ▪ Periodontal complications; oral infections; mucosal associated lymphoid tissue (MALT) lymphoma DIAGNOSIS ▪ Clinical presentation: persistent dry eyes/ mouth, parotid gland enlargement DIAGNOSTIC IMAGING Parotid gland MRI ▪ Honeycomb pattern Salivary gland ultrasound ▪ Multiple hypoechoic areas LAB RESULTS ▪ CBC ▫ Leukopenia, thrombocytopenia, anemia ▪ ↑ ESR ▪ Urinalysis OSMOSIS.ORG 647
▫ Proteinuria/hematuria reflecting glomerulonephritis ▪ Labial salivary gland biopsy (confirm diagnosis) ▫ Focal lymphocyte foci (collections of tightly aggregated lymphocytes) ▪ Serologic tests (support diagnosis) ▫ ↑ antinuclear antibodies (ANAs) in 95% of individuals ▫ ↑ rheumatoid factor (RF) in 50–75% of individuals with/without rheumatoid arthritis ▫ Anti-Sjögren syndrome A (SSA) (Ro), Anti-Sjögren syndrome B (SSB) (La) specific to SS, found elevated only in 55%, 40% of individuals, respectively OTHER DIAGNOSTICS Tear deficiency tests ▪ Schirmer test ▫ Measures reflex tear production; wetting of test paper < 5mm indicative of tear deficiency ▫ Ocular surface staining with Rose Bengal stain and slit-lamp examination—assess tear break-up time (TBUT); TBUT < 10 seconds indicative of tear deficiency ▪ Salivary gland tests ▫ Salivary gland scintigraphy: low uptake of radionuclide characteristic of SS ▫ Sialometry: low volume of saliva indicative of salivary gland hypofunction 648 OSMOSIS.ORG Figure 112.5 A lymphocytic infiltrate in a minor salivary gland excised from an individual with Sjögren’s syndrome. TREATMENT MEDICATIONS ▪ Mild SS ▫ Secretagogues ▫ Local treatment for ocular, oral dryness (e.g. artificial tears) ▪ Moderate to severe SS ▫ Immunosuppressive treatment
Chapter 112 Inflammatory Connective Tissue Disorders SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATHOLOGY & CAUSES ▪ Chronic systemic autoimmune disorder; wide range of clinical, serological features ▪ Periods of flare-ups, remittance ▪ Environmental triggers damage DNA → apoptosis → release of nuclear bodies ▪ Clearance of apoptotic bodies ineffective due to genetic defects → increased amount of nuclear antigens in bloodstream → initiates immune response → production of antinuclear antibodies → bind to antigens, form immune complexes ▪ Complexes deposit in tissues (e.g. kidneys, skin, joints, heart) → Type III hypersensitivity reaction ▪ Individuals may develop antibodies targeting molecules (e.g., phospholipids) of red, white blood cells → marking them for phagocytosis → Type II hypersensitivity reaction ▪ Antiphospholipid syndrome ▫ Hypercoagulable state; individuals prone to develop clots (e.g. deep vein thrombosis, hepatic vein thrombosis, stroke) SIGNS & SYMPTOMS ▪ Fever, joint pain, rash in sun-exposed areas ▪ Typical rashes ▫ Malar rash (butterfly rash): over cheeks ▫ Discoid rash: plaque-like/patchy redness, can scar ▫ General photosensitivity: typically lasts few days RISK FACTORS Genetic defects associated with SLE UV radiation Smoking Viral, bacterial infections Medications (e.g. procainamide, hydralazine, isoniazid, estrogens) ▪ More common in individuals who are biologically female, of reproductive age ▪ ▪ ▪ ▪ ▪ COMPLICATIONS ▪ Cardiovascular disease ▫ Libman–Sacks endocarditis, myocardial infarction (MI) ▪ Serious infections; renal failure; hypertension Figure 112.6 A butterfly rash on the face of an individual with systemic lupus erythematosus. OSMOSIS.ORG 649
▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ Weight loss Ulcers in oral/nasal mucosa Serositis (e.g. pleuritis/pericarditis) Libman–Sacks endocarditis: formation of nonbacterial vegetations on ventricular, atrial valve surfaces; mitral, aortic valves (most common) Myocarditis Renal disorders ▫ Abnormal levels of urine protein, diffuse proliferative glomerulonephritis Neurologic disorders ▫ Seizures, psychosis Hematologic disorders ▫ Anemia, thrombocytopenia, leukopenia DIAGNOSIS OTHER DIAGNOSTICS Diagnostic criteria (4 of 11) ▪ Malar rash ▪ Discoid rash ▪ General photosensitivity ▪ Oral/nasal ulcers ▪ Serositis ▪ Arthritis in ≥ two joints ▪ Renal disorders ▪ Neurologic disorders ▪ Hematologic disorders ▪ Antinuclear antibodies ▫ Very sensitive, not specific ▪ Other antibodies ▫ SLE specific: anti-Smith, anti-dsDNA ▫ Anti-phospholipid: anticardiolipin (false-positive test for syphilis); lupus anticoagulant (lupus antibody); anti-beta 2 glycoprotein I TREATMENT ▪ Goal: prevent relapses, limit severity MEDICATIONS Figure 112.7 An MRI scan of the head of an individual with SLE who presented with altered mental status and seizures. There a numerous small infarcts suggestive of cerebral vasculitis. The individual improved after treatment with steroids. 650 OSMOSIS.ORG ▪ Long term therapy ▫ Antimalarial agents ▪ Mild to moderate manifestations ▫ Non-steroidal anti-inflammatory drugs (NSAIDs), low doses of corticosteroids ▪ Severe/life-threatening manifestations ▫ High doses of corticosteroids, intensive immunosuppressive drugs OTHER INTERVENTIONS ▪ ▪ ▪ ▪ ▪ Avoid sun exposure Physical exercise Balanced diet Smoking cessation Immunizations
Chapter 112 Inflammatory Connective Tissue Disorders Figure 112.8 A histological section of a lymph node from an individual with lupus lymphadenopathy. There is necrosis, with an absence of neutrophils, and large numbers of hematoxylin bodies. Figure 112.9 Histological appearance of the glomerulus in a case of lupus nephritis. There is global mesangial cell proliferation and abundant mesangial matrix. OSMOSIS.ORG 651

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This Osmosis High-Yield Note provides an overview of Inflammatory connective tissue disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Inflammatory connective tissue disorders by visiting the associated Learn Page.