Chapter 11_1 flashcards

Question 1

Allergic Rhinitis (Type I Hypersensitivity): Definition & Pathophysiology

Answer 1

A Type I immediate hypersensitivity response to environmental allergens (e.g., pollen, animal dander, dust). Exposure triggers IgE production, which binds to mast cells. Re-exposure causes mast cell degranulation, releasing histamine and other mediators, leading to vasodilation, increased permeability, smooth muscle constriction, and mucus hypersecretion in the nasal passages.

Question 2

Allergic Rhinitis: Clinical Presentation, Diagnosis & Treatment

Answer 2

Clinical: Sneezing, rhinorrhea (watery, clear discharge), nasal congestion, itchy/watery eyes (conjunctivitis), cough, possible bronchospasm. Pale nasal mucosa. Nasal polyps in chronic cases.
Diagnosis: Clinical history, presence of eosinophils in nasal secretions, positive skin tests for specific allergens, IgE serology testing (ELISA, RAST).
Treatment: Allergen avoidance, antihistamines, intranasal corticosteroids, decongestants.

Question 3

Urticaria (Hives): Definition & Association

Answer 3

A skin rash characterized by itchy, raised welts (wheals). It is a common manifestation of Type I immediate hypersensitivity reactions (allergies) but can have other causes. Often seen in allergic reactions and can be a sign of systemic anaphylaxis.

Question 4

Angioedema: Definition & Significance

Answer 4

Swelling of the deeper dermal or subcutaneous/submucosal tissues, often affecting the face, lips, mouth, tongue, larynx, and periorbital regions. Can be a feature of severe Type I hypersensitivity reactions like anaphylaxis and can compromise the airway.

Question 5

Bronchial Asthma (related to Type I Hypersensitivity)

Answer 5

A chronic inflammatory disorder of the airways characterized by reversible bronchoconstriction, airway inflammation, and mucus production. Allergic asthma is a common form, triggered by Type I hypersensitivity reactions to inhaled allergens, leading to bronchospasm.

Question 6

Allergic Gastroenteritis (related to Type I Hypersensitivity)

Answer 6

A Type I immediate hypersensitivity reaction occurring in the gastrointestinal tract due to ingestion of food allergens (e.g., shellfish, peanuts, milk). Involves IgE-mediated mast cell degranulation in the GI mucosa, leading to symptoms like nausea, vomiting, diarrhea, and abdominal pain.

Question 7

Systemic Anaphylaxis / Anaphylactic Shock: Definition & Pathophysiology

Answer 7

A severe, life-threatening, systemic Type I immediate hypersensitivity reaction. An overwhelming allergic response to an allergen (even in small doses) causes widespread mast cell degranulation. Massive release of histamine and other mediators leads to systemic vasodilation, increased vascular permeability, bronchoconstriction, and laryngeal edema. Anaphylactic shock occurs when hypotension becomes severe.

Question 8

Systemic Anaphylaxis: Clinical Presentation & Treatment

Answer 8

Clinical: Rapid onset: itching, urticaria, erythema, angioedema (lips, tongue, face), bronchoconstriction (stridor, wheezing, dyspnea), laryngeal edema, profound hypotension, tachycardia, loss of consciousness.
Treatment: MEDICAL EMERGENCY. Immediate epinephrine (IM/IV). Antihistamines, corticosteroids. Airway management, oxygen, IV fluids. Cardiac monitoring.

Question 9

Transfusion Reaction (Type II Cytotoxic Hypersensitivity)

Answer 9

A classic Type II hypersensitivity reaction where Igs (usually IgM or IgG) in the recipient’s blood react with antigens on the surface of transfused donor red blood cells (e.g., ABO incompatibility). This leads to antibody-mediated cell destruction (hemolysis) and phagocytosis.

Question 10

Contact Dermatitis (Type IV Delayed Hypersensitivity)

Answer 10

An inflammatory skin reaction occurring days after exposure to an antigen to which T lymphocytes have been previously sensitized. Examples include reactions to poison ivy (vesicular, erythematous rash) or certain metals (nickel). The delay is due to the time taken for T cells to migrate and mount a response.

Question 11

Autoimmune Disease (General Concept)

Answer 11

A condition where the immune system loses self-tolerance and mistakenly attacks the body’s own cells and tissues (self-antigens) as if they were foreign. This involves T cells or the production of autoantibodies, leading to inflammation and organ damage.

Question 12

Molecular Mimicry (Mechanism in Autoimmunity)

Answer 12

A proposed mechanism for some autoimmune diseases where an infectious agent possesses antigens that are structurally similar (mimic) to self-antigens. The immune response generated against the pathogen cross-reacts with the body’s own tissues that have these similar antigens.

Question 13

Systemic Lupus Erythematosus (SLE): Definition & Etiology

Answer 13

Definition: A chronic, multisystem autoimmune disease characterized by the production of autoantibodies, particularly antinuclear antibodies (ANAs), against components of the cell nucleus and other self-antigens. Features remissions and exacerbations.
Etiology: Unknown; involves genetic predisposition (HLA genes, complement deficiencies, TREX1), environmental triggers (UV light, EBV infection, drugs like hydralazine, procainamide), and hormonal factors (estrogen).

Question 14

Systemic Lupus Erythematosus (SLE): Pathophysiology

Answer 14

Formation of autoantibodies (e.g., anti-dsDNA, anti-Sm, anti-Ro, antiphospholipid). These antibodies form immune complexes with self-antigens, which deposit in various tissues (skin, joints, kidneys, blood vessels, lungs, CNS). This deposition activates complement and triggers inflammation, leading to microvasculature damage and organ dysfunction.

Question 15

Systemic Lupus Erythematosus (SLE): Clinical Presentation

Answer 15

Highly variable.
Constitutional: Fever, fatigue, weight loss.
Musculoskeletal: Arthralgias, arthritis (90%), myalgias.
Cutaneous: Malar (butterfly) rash, discoid rash, photosensitivity, oral/nasal ulcers, alopecia.
Renal: Lupus nephritis (proteinuria, hematuria, hypertension).
Other: Pleuritis, pericarditis, vasculitis, Raynaud’s phenomenon, neuropsychiatric symptoms (seizures, psychosis), hematological (anemia, leukopenia, thrombocytopenia).

Question 16

Systemic Lupus Erythematosus (SLE): Diagnosis

Answer 16

Based on clinical features (2019 EULAR/ACR criteria: ANA positivity + score =10).
Labs: ANA (positive in >95%), anti-dsDNA and anti-Sm (more specific), antiphospholipid antibodies, anti-Ro, low C3/C4, elevated ESR/CRP. CBC (cytopenias), urinalysis.
Biopsy: Skin or kidney biopsy can be diagnostic.

Question 17

Systemic Lupus Erythematosus (SLE): Treatment

Answer 17

Non-pharmacologic: Sun protection, diet, exercise, smoking cessation.
Pharmacologic: Hydroxychloroquine (for all patients unless contraindicated), NSAIDs, corticosteroids (short-term/low-dose if possible). Immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide for severe disease/lupus nephritis). Biologics (belimumab, anifrolumab).

Question 18

Lupus Nephritis

Answer 18

Kidney inflammation in SLE caused by the deposition of immune complexes in the glomeruli. Can lead to proteinuria, hematuria, hypertension, nephrotic syndrome, and potentially end-stage renal disease. A major cause of morbidity and mortality in SLE.

Question 19

Rheumatoid Arthritis (RA): Definition & Etiology

Answer 19

Definition: A chronic, systemic autoimmune inflammatory disorder primarily targeting synovial joints, causing symmetric polyarthritis, joint destruction, deformity, and functional disability. Can have extra-articular manifestations.
Etiology: Unknown; involves genetic susceptibility (HLA-DRB1, PTPN22, PAD14), environmental factors (smoking, infections like Porphyromonas gingivalis, EBV), hormonal and immunological factors.

Question 20

Rheumatoid Arthritis (RA): Pathophysiology

Answer 20

Autoimmune attack on synovial tissues. APCs activate T cells, which release cytokines. B cells mature into plasma cells producing autoantibodies: Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (ACPAs). Inflammatory mediators (TNF-alpha, ILs) perpetuate inflammation, leading to synovial hypertrophy (pannus formation), cartilage degradation, and bone erosion by osteoclasts.

Question 21

Rheumatoid Arthritis (RA): Clinical Presentation

Answer 21

Joints: Symmetrical, tender, swollen joints (MCP, PIP joints of hands, wrists, MTP joints of feet common). Morning stiffness >30-60 minutes.
Deformities: Boutonnière, swan neck, ulnar deviation, Baker’s cyst (popliteal).
Systemic: Fatigue, fever, malaise, weight loss, rheumatoid nodules.
Extra-articular: Vasculitis, pericarditis, pleuritis, interstitial lung disease, scleritis, carpal tunnel syndrome, Felty’s syndrome, osteoporosis. Accelerated atherosclerosis.

Question 22

Rheumatoid Arthritis (RA): Diagnosis

Answer 22

Based on clinical features (ACR/EULAR 2010 criteria: score =6/10).
Labs: Elevated ESR, CRP. RF (positive in ~70%), ACPAs (positive in ~70%, more specific and prognostic).
Imaging: X-rays show joint space narrowing, erosions, osteopenia. Ultrasound/MRI can detect synovitis earlier.

Question 23

Rheumatoid Arthritis (RA): Treatment

Answer 23

Goal: Remission or low disease activity.
Non-pharmacologic: Education, PT/OT, exercise, joint protection.
Pharmacologic: DMARDs (Disease-Modifying Antirheumatic Drugs) are cornerstone. Methotrexate (MTX) is first-line. Other conventional DMARDs: sulfasalazine, leflunomide, hydroxychloroquine.
Biologic DMARDs (TNF inhibitors: etanercept, adalimumab; IL-6 inhibitor: tocilizumab; T-cell co-stimulation modulator: abatacept; B-cell depletor: rituximab).
Targeted synthetic DMARDs (Janus Kinase (JAK) inhibitors: tofacitinib, baricitinib).
NSAIDs and glucocorticoids for symptom control/flares.

Question 24

Baker’s Cyst (Popliteal Cyst)

Answer 24

A fluid-filled sac behind the knee, often causing a bulge and a feeling of tightness. Commonly associated with conditions causing knee joint swelling, such as rheumatoid arthritis or osteoarthritis. It’s a distension of the gastrocnemio-semimembranosus bursa.

Question 25

Felty's Syndrome

Answer 25

A rare, severe manifestation of rheumatoid arthritis characterized by the triad of: 1. Rheumatoid arthritis 2. Splenomegaly (enlarged spleen) 3. Neutropenia (low white blood cell count, specifically neutrophils), leading to increased risk of infections.

Question 26

Sarcoidosis: Definition & Pathophysiology

Answer 26

Definition: A chronic, multisystem autoimmune disorder of unknown origin, characterized by the formation of non-caseating epithelioid granulomas in various organs, most commonly the lungs and lymph nodes. Pathophysiology: An exaggerated cell-mediated immune response to an unidentified antigen(s). Macrophages and T lymphocytes (CD4+ and CD8+) accumulate, with release of cytokines (TNF-alpha, ILs), leading to granuloma formation which can disrupt organ structure and function.

Question 27

Sarcoidosis: Clinical Presentation

Answer 27

Highly variable. General: Fever, fatigue, malaise, anorexia, weight loss. Pulmonary (>90%): Cough, dyspnea, chest discomfort, wheezes (interstitial lung disease). Cutaneous: Erythema nodosum (tender red nodules, usually on shins), lupus pernio (violaceous plaques on face, ears, nose), maculopapular rashes. Ocular: Uveitis, retinitis, dry eyes. Other: Arthritis, parotid gland enlargement, lymphadenopathy, Heerfordt's syndrome (uveoparotid fever), Löfgren's syndrome (fever, bilateral hilar lymphadenopathy, arthritis, EN), hypercalcemia, neurological involvement.

Question 28

Sarcoidosis: Diagnosis

Answer 28

Based on: 1) Compatible clinical/radiological findings; 2) Histopathological evidence of non-caseating epithelioid granulomas from biopsy (e.g., lymph node, skin, transbronchial); 3) Exclusion of other diseases with similar findings. Imaging: Chest X-ray/CT (bilateral hilar lymphadenopathy is hallmark, interstitial infiltrates). Labs: Elevated serum angiotensin-converting enzyme (ACE) levels (non-specific). Hypercalcemia/hypercalciuria. PFTs (often restrictive pattern).

Question 29

Sarcoidosis: Treatment

Answer 29

Observation if asymptomatic. Pharmacologic (for symptomatic/progressive disease): Corticosteroids (prednisone) are mainstay. Steroid-sparing agents/immunosuppressants (methotrexate, azathioprine, leflunomide, mycophenolate). Antimalarials (hydroxychloroquine for skin/joint). TNF-alpha inhibitors (infliximab, adalimumab) for refractory or severe cases. Lifestyle modifications.

Question 30

Erythema Nodosum (EN)

Answer 30

An inflammatory condition characterized by tender, erythematous (red) nodules, typically found on the anterior surface of the legs (shins). It's considered a Type IV hypersensitivity reaction. Can be a manifestation of sarcoidosis, Sjögren's syndrome, IBD, infections (e.g., streptococcal), and certain drugs.

Question 31

Lupus Pernio

Answer 31

A specific dermatological manifestation of sarcoidosis, characterized by chronic, indurated, violaceous or purplish plaques and nodules, typically on the nose, cheeks, ears, and fingers. Associated with more severe, chronic sarcoidosis.

Question 32

Löfgren’s Syndrome

Answer 32

An acute form of sarcoidosis with a clinically distinct presentation, characterized by the triad of: 1. Fever 2. Bilateral hilar lymphadenopathy 3. Arthritis (often ankles) May also include erythema nodosum. Generally has a good prognosis.

Question 33

Heerfordt’s Syndrome (Uveoparotid Fever)

Answer 33

A specific subtype of sarcoidosis characterized by the combination of: 1. Facial nerve palsy (or trigeminal nerve involvement) 2. Parotid gland enlargement 3. Anterior uveitis 4. Low-grade fever

Question 34

Sjögren’s Syndrome (SS): Definition & Pathophysiology

Answer 34

Definition: A chronic autoimmune disease primarily affecting exocrine glands (especially lacrimal and salivary), leading to their destruction and characteristic symptoms of dryness. Can be primary or secondary (with RA, SLE). Pathophysiology: Lymphocytic infiltration (T cells, B cells, plasma cells) of exocrine glands. Ductal epithelial cells show hyperplasia, obstructing ducts. This leads to glandular fibrosis, atrophy, and reduced secretions (tears, saliva).

Question 35

Sjögren’s Syndrome (SS): Clinical Presentation (Sicca & Systemic)

Answer 35

Sicca Symptoms: Xerostomia (dry mouth): Difficulty swallowing, speaking, increased dental caries. Keratoconjunctivitis sicca (dry eyes): Burning, itching, gritty sensation, blurred vision. Systemic/Extraglandular: Fatigue, fibromyalgia, arthralgias/arthritis, Raynaud's, dry skin, cutaneous vasculitis, parotid gland enlargement, peripheral neuropathy, pulmonary fibrosis, nephritis, thyroid disease. Increased risk of B-cell lymphoma.

Question 36

Sjögren’s Syndrome (SS): Diagnosis & Treatment

Answer 36

Diagnosis: Clinical symptoms + objective tests. ACR/EULAR classification criteria. Autoantibodies: ANA, anti-Ro/SSA, anti-La/SSB. RF may be positive. Ophthalmologic tests: Schirmer test (tear production), ocular surface staining. Salivary gland biopsy (lip biopsy showing focal lymphocytic sialadenitis). Treatment: Symptomatic relief (artificial tears, saliva substitutes, sialogogues like pilocarpine/cevimeline). Manage extraglandular manifestations (hydroxychloroquine, corticosteroids, immunosuppressants like methotrexate, rituximab for severe cases).

Question 37

Keratoconjunctivitis Sicca

Answer 37

Dryness of the conjunctiva and cornea due to deficient tear production or excessive tear evaporation. A hallmark symptom of Sjögren's Syndrome, leading to eye irritation, burning, grittiness, and potential visual impairment.

Question 38

Xerostomia

Answer 38

Dry mouth resulting from reduced or absent saliva flow. A hallmark symptom of Sjögren's Syndrome. It can cause difficulty speaking, swallowing, altered taste, and an increased risk of dental caries and oral infections.

Question 39

Scleroderma (Systemic Sclerosis - SSc): Definition & Pathophysiology

Answer 39

Definition: A chronic autoimmune disease characterized by widespread microangiopathy, inflammation, autoimmunity, and abnormal accumulation of fibrous tissue (collagen deposition leading to fibrosis) in the skin and internal organs (e.g., GI tract, lungs, kidneys, heart). Pathophysiology: Endothelial cell injury and activation, fibroblast activation leading to excessive collagen production, and immune dysregulation (T cells, B cells, autoantibodies).

Question 40

Scleroderma (SSc): Clinical Presentation (Cutaneous & Systemic)

Answer 40

Cutaneous: Skin thickening and hardening (scleroderma), often starting in fingers (sclerodactyly) and face (mask-like facies). Can be limited or diffuse. Puffy fingers. Vascular: Raynaud's phenomenon (very common), telangiectasias, digital ulcers. GI: Esophageal dysmotility (GERD, dysphagia), gastric antral vascular ectasia (GAVE), malabsorption. Pulmonary: Interstitial lung disease (fibrosis), pulmonary arterial hypertension (PAH). Renal: Scleroderma renal crisis (abrupt onset hypertension, kidney failure). Musculoskeletal: Arthralgia, myalgia, joint contractures. Cardiac: Myocardial fibrosis, pericarditis, arrhythmias. CREST Syndrome: Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasias.

Question 41

Scleroderma (SSc): Diagnosis & Treatment

Answer 41

Diagnosis: Clinical findings (skin changes, Raynaud's). ACR/EULAR classification criteria. Autoantibodies: ANA, anti-centromere (often in limited SSc/CREST), anti-topoisomerase I (Scl-70, often in diffuse SSc), anti-RNA polymerase III. Nailfold capillaroscopy. Treatment: No cure; organ-specific and symptomatic. Raynaud's: Calcium channel blockers. GERD: PPIs. Skin: Immunosuppressants (methotrexate, mycophenolate). ILD: Cyclophosphamide, mycophenolate, nintedanib, tocilizumab. PAH: Vasodilators. Renal crisis: ACE inhibitors.

Question 42

CREST Syndrome (Limited Cutaneous Systemic Sclerosis)

Answer 42

A subtype of scleroderma (systemic sclerosis) characterized by: Calcinosis (calcium deposits in skin) Raynaud’s phenomenon Esophageal dysmotility Sclerodactyly (thickening/tightening of skin on fingers/toes) Telangiectasias (dilated small blood vessels on skin) Often associated with anti-centromere antibodies.

Question 43

Gastroesophageal Reflux Disease (GERD) in Scleroderma

Answer 43

A common complication of scleroderma due to esophageal dysmotility (impaired peristalsis and lower esophageal sphincter function) caused by fibrosis of the esophageal wall. Leads to heartburn, regurgitation, and potential complications like esophagitis or strictures.

Question 44

Pulmonary Fibrosis / Pulmonary Arterial Hypertension in Scleroderma

Answer 44

Pulmonary Fibrosis (Interstitial Lung Disease - ILD): Scarring of lung tissue, leading to restrictive lung disease, dyspnea, and cough. A major cause of mortality in SSc. Pulmonary Arterial Hypertension (PAH): High blood pressure in the arteries of the lungs, leading to right heart failure. Can occur with or without ILD.

Question 45

Raynaud’s Phenomenon

Answer 45

Episodic vasospasm of small arteries, usually in the fingers and toes, triggered by cold or stress. Characterized by a triphasic color change: pallor (white), cyanosis (blue), and rubor (red) upon rewarming. Common in scleroderma, SLE, and other connective tissue diseases.

Question 46

Polyarteritis Nodosa (PAN): Definition & Pathophysiology

Answer 46

Definition: A systemic necrotizing vasculitis affecting medium-sized muscular arteries (spares venules, arterioles, capillaries, and typically the lungs). Often involves renal and visceral arteries. Pathophysiology: Inflammation of blood vessel walls, leading to stenosis, thrombosis, aneurysm formation, and rupture. Tissue ischemia and infarction occur distal to affected vessels. Immune complex deposition is implicated; can be associated with Hepatitis B/C.

Question 47

Polyarteritis Nodosa (PAN): Clinical Presentation, Diagnosis & Treatment

Answer 47

Clinical: Fever, weight loss, malaise, myalgias, arthralgias. Skin lesions (nodules, purpura, ulcers, livedo reticularis), peripheral neuropathy (mononeuritis multiplex), abdominal pain (mesenteric ischemia), hypertension (renal artery involvement), renal insufficiency. Diagnosis: Biopsy of affected tissue (e.g., skin, nerve, muscle) showing necrotizing vasculitis. Angiography showing aneurysms and stenoses in medium-sized arteries. Elevated ESR/CRP. Treatment: High-dose corticosteroids. Cyclophosphamide or other immunosuppressants (azathioprine, methotrexate) for severe disease. Antivirals if Hepatitis B/C positive.

Question 48

Type 1 Diabetes (as Autoimmune Disease)

Answer 48

An organ-specific autoimmune disease where the body's T cells and autoantibodies attack and destroy the insulin-producing beta cells in the pancreas. This results in absolute insulin deficiency, requiring lifelong insulin therapy.

Question 49

Multiple Sclerosis (MS) (as Autoimmune Disease)

Answer 49

An autoimmune disease where the body's T cells attack myelin, the protective sheath covering nerve fibers in the central nervous system (CNS). This demyelination leads to impaired nerve signal transmission, resulting in a wide range of neurological symptoms like motor weakness, sensory loss, gait disturbance, and visual problems.

Question 50

Rheumatic Fever / Rheumatic Heart Disease

Answer 50

Rheumatic Fever: An inflammatory disease that can develop after a Group A beta-hemolytic streptococcal (GABHS) infection (strep throat). Caused by molecular mimicry, where antibodies produced against streptococcal antigens cross-react with host tissues, particularly heart, joints, brain, and skin. Rheumatic Heart Disease: Chronic heart valve damage (especially mitral and aortic valves) resulting from one or more episodes of acute rheumatic fever. Leads to valvular stenosis or regurgitation.

Question 51

Immunodeficiency (General Concept)

Answer 51

A state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Can be: Primary (Congenital): Genetically determined, usually manifesting in infancy/childhood. Secondary (Acquired): Develops later in life due to external factors (e.g., HIV, malnutrition, immunosuppressive drugs).

Question 52

Severe Combined Immunodeficiency Disease (SCID): Definition & Pathophysiology

Answer 52

Definition: A group of rare, life-threatening genetic disorders characterized by profound defects in both T-lymphocyte and B-lymphocyte function (combined immunodeficiency). Some forms also affect NK cells. Pathophysiology: Various genetic mutations (e.g., X-linked SCID affecting common gamma chain, ADA deficiency) disrupt lymphocyte development or function, leading to a near-complete absence of adaptive immunity.

Question 53

Severe Combined Immunodeficiency Disease (SCID): Clinical Presentation, Diagnosis & Treatment

Answer 53

Clinical: Presents in early infancy (first few months) with severe recurrent infections (viral, bacterial, fungal, protozoal), *Pneumocystis jirovecii* pneumonia, chronic diarrhea, failure to thrive, persistent oral candidiasis. Life-threatening without treatment. Diagnosis: Newborn screening (TREC assay for T-cell receptor excision circles). Markedly low lymphocyte counts (especially T cells), absent/low immunoglobulins, poor/absent vaccine responses. Treatment: Hematopoietic stem cell transplantation (HSCT) is curative. Enzyme replacement therapy (for ADA-SCID). Gene therapy. Protective isolation, prophylactic antimicrobials. Live vaccines contraindicated.

Question 54

Selective IgA Deficiency (sIgAD): Definition & Pathophysiology

Answer 54

Definition: The most common primary immunodeficiency, characterized by a significantly decreased or absent level of serum immunoglobulin A (IgA), with normal levels of IgG and IgM, and intact T-cell function. Pathophysiology: Defect in B-cell differentiation into IgA-producing plasma cells. Specific cause often unknown; can be genetic or acquired (drugs, infections). IgA is crucial for mucosal immunity.

Question 55

Selective IgA Deficiency (sIgAD): Clinical Presentation, Diagnosis & Treatment

Answer 55

Clinical: Many are asymptomatic. Increased susceptibility to recurrent sinopulmonary infections (otitis media, sinusitis, bronchitis, pneumonia), GI infections (Giardia), and GI disorders (celiac disease, IBD). Higher incidence of autoimmune diseases and allergies. Anaphylactic reactions to blood products containing IgA can occur. Diagnosis: Serum IgA level < 7 mg/dL (in patients >4 years) with normal IgG, IgM, and normal antibody responses to vaccines. Treatment: Often no specific treatment if asymptomatic. Prophylactic antibiotics for recurrent infections. IVIG is generally NOT indicated (contains little IgA and risk of anti-IgA antibodies). Avoid IgA-containing blood products if sensitized.

Question 56

Chronic Mucocutaneous Candidiasis (CMCC): Definition & Pathophysiology

Answer 56

Definition: A group of disorders characterized by persistent or recurrent *Candida* (yeast) infections of the skin, nails, and mucous membranes. Not usually invasive. Often associated with autoimmune endocrine disorders (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy - APECED). Pathophysiology: Selective T-cell defect in responding to *Candida albicans*. Can be due to mutations in genes like AIRE (causing APECED) or STAT1, or autoantibodies against cytokines like IL-17 or IL-22 which are crucial for anti-Candida immunity.

Question 57

Chronic Mucocutaneous Candidiasis (CMCC) / APECED: Clinical Presentation, Diagnosis & Treatment

Answer 57

Clinical: Persistent oral thrush, *Candida* infections of skin (dermatitis) and nails (onycholysis). APECED triad: CMCC, hypoparathyroidism (leading to hypocalcemia), and adrenal insufficiency (Addison's disease). Other autoimmune conditions (thyroid disease, type 1 diabetes, etc.). Diagnosis: Clinical picture of chronic candidiasis. Genetic testing for AIRE, STAT1 mutations. Evaluation for associated endocrinopathies and autoantibodies (e.g., against IFN-alpha, IL-17, IL-22). Treatment: Long-term antifungal therapy (e.g., fluconazole). Treatment of associated endocrinopathies (e.g., calcium/vitamin D for hypoparathyroidism, corticosteroids for adrenal insufficiency). Janus kinase inhibitors (ruxolitinib, baricitinib) show promise. Immunoglobulin replacement if severe antibody deficiency.

Question 58

Hypoparathyroidism (in CMCC/APECED)

Answer 58

Underactivity of the parathyroid glands, leading to insufficient parathyroid hormone (PTH) production. This results in low blood calcium levels (hypocalcemia) and high blood phosphate levels. Symptoms can include muscle cramps, tetany, and seizures. A key feature of the APECED triad in Chronic Mucocutaneous Candidiasis.

Question 59

Adrenal Failure / Adrenal Insufficiency (in CMCC/APECED)

Answer 59

Inability of the adrenal glands to produce sufficient steroid hormones (primarily cortisol and sometimes aldosterone). Leads to symptoms like fatigue, weakness, weight loss, low blood pressure. Autoimmune destruction of the adrenal glands (Addison's disease) is a key feature of the APECED triad in Chronic Mucocutaneous Candidiasis.

Question 60

Hypogammaglobulinemia: Definition & Causes

Answer 60

Definition: A condition characterized by abnormally low levels of one or more classes of immunoglobulins (antibodies) in the blood, leading to an impaired immune response and increased susceptibility to infections. Causes: Primary: Genetic defects in B-cell development or function (e.g., X-linked agammaglobulinemia, Common Variable Immunodeficiency). Secondary: Acquired due to other conditions or treatments, such as hematologic malignancies (leukemia, lymphoma), immunosuppressive drugs (rituximab, corticosteroids), protein loss (nephrotic syndrome, protein-losing enteropathy), severe burns.

Question 61

Hypogammaglobulinemia: Clinical Presentation, Diagnosis & Treatment

Answer 61

Clinical: Recurrent bacterial infections, especially sinopulmonary (pneumonia, sinusitis, otitis media) caused by encapsulated bacteria (*S. pneumoniae, H. influenzae*). GI infections, diarrhea, malabsorption. Failure to thrive in children. Diagnosis: Quantitative measurement of serum immunoglobulins (IgG, IgA, IgM) showing levels below age-appropriate norms. Assessment of antibody response to vaccines. Treatment: Immunoglobulin replacement therapy (IVIG or subcutaneous Ig). Prophylactic antibiotics. Management of underlying cause if secondary. Live vaccines often contraindicated.

Question 62

Wiskott-Aldrich Syndrome (WAS): Definition & Pathophysiology

Answer 62

Definition: A rare X-linked recessive primary immunodeficiency disorder characterized by a triad of eczema, thrombocytopenia (low platelets, often small in size), and recurrent infections. Pathophysiology: Caused by mutations in the WASP gene, which encodes for Wiskott-Aldrich syndrome protein (WASp). WASp is crucial for actin cytoskeleton regulation in hematopoietic cells, affecting T-cell and B-cell function, platelet formation, and immune synapse formation. Leads to combined immunodeficiency (defective T-cell and B-cell responses, low IgM).

Question 63

Wiskott-Aldrich Syndrome (WAS): Clinical Presentation

Answer 63

Thrombocytopenia: Bleeding (petechiae, purpura, epistaxis, bloody diarrhea, prolonged bleeding from circumcision). Eczema: Often severe and difficult to treat. Recurrent Infections: Sinopulmonary infections (bacteria), opportunistic infections (*P. jirovecii*, viral infections like HSV, CMV). Autoimmunity: Common (autoimmune hemolytic anemia, vasculitis, IBD, arthritis). Malignancy: Increased risk of B-cell lymphomas and leukemia later in life.

Question 64

Wiskott-Aldrich Syndrome (WAS): Diagnosis & Treatment

Answer 64

Diagnosis: Clinical triad. WASP gene mutation analysis. Low platelet count, small platelet volume. Variable Ig levels (typically low IgM, elevated IgA/IgE, normal/low IgG). Impaired T-cell function (anergy). Treatment: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. Prophylactic antibiotics and IVIG. Platelet transfusions for bleeding. Treatment of eczema and autoimmune complications. Splenectomy (can increase platelet count but increases sepsis risk). Live vaccines contraindicated.

Question 65

DiGeorge Syndrome (22q11.2 Deletion Syndrome): Definition & Pathophysiology

Answer 65

Definition: A primary immunodeficiency disorder caused by a microdeletion on chromosome 22 (22q11.2), resulting in developmental defects of the 3rd and 4th pharyngeal pouches. This leads to a spectrum of abnormalities. Pathophysiology: The deletion affects the development of several structures, including the thymus (leading to T-cell deficiency of varying severity), parathyroid glands (hypoparathyroidism and hypocalcemia), and heart (congenital cardiac defects).

Question 66

DiGeorge Syndrome: Clinical Presentation (CATCH-22)

Answer 66

Highly variable presentation, often remembered by CATCH-22 mnemonic: Cardiac defects (e.g., Tetralogy of Fallot, interrupted aortic arch, VSDs) (80%). Abnormal facies (micrognathia, hypertelorism, low-set ears, shortened philtrum, cleft palate). Thymic hypoplasia/aplasia (impaired T-cell immunity, recurrent infections). Cleft palate (or other palatal abnormalities). Hypocalcemia/Hypoparathyroidism (due to parathyroid hypoplasia, can cause tetany, seizures). Also developmental delay, learning difficulties, increased risk of autoimmune disorders.

Question 67

DiGeorge Syndrome: Diagnosis & Treatment

Answer 67

Diagnosis: Detection of 22q11.2 deletion by FISH or chromosomal microarray. Clinical features. Evaluation of T-cell numbers/function, serum calcium/PTH, echocardiogram. Treatment: Multidisciplinary approach. Management of cardiac defects (surgery). Calcium/Vitamin D for hypocalcemia. Prophylactic antibiotics and IVIG for significant immunodeficiency. Thymus transplantation or HSCT for complete DiGeorge (no thymic function). Speech/developmental therapy. Live vaccines often contraindicated depending on immune status.

Question 68

Hypocalcemic Tetany (in DiGeorge Syndrome)

Answer 68

A state of increased neuromuscular excitability caused by low blood calcium levels (hypocalcemia), which can result from hypoparathyroidism in DiGeorge Syndrome. Manifests as muscle cramps, spasms (especially of hands and feet - carpopedal spasm), laryngospasm, and potentially seizures.

Question 69

Congenital Cardiac Abnormalities (in DiGeorge Syndrome)

Answer 69

Structural heart defects present at birth, a common feature of DiGeorge Syndrome (approx. 80% of patients). Examples include Tetralogy of Fallot, ventricular septal defects (VSDs), truncus arteriosus, and interrupted aortic arch. These often require surgical correction.

Question 70

Human Immunodeficiency Virus (HIV) Infection: Definition & Target

Answer 70

Definition: Infection with HIV, a retrovirus (genus *Lentivirus*) that attacks and progressively destroys the human immune system, primarily CD4+ T-lymphocytes (helper T cells). This leads to immunodeficiency, making the host susceptible to opportunistic infections and cancers. Target Cells: Primarily CD4+ T cells. Also infects macrophages, dendritic cells, and other cells expressing the CD4 receptor and co-receptors CCR5 or CXCR4.

Question 71

HIV Pathophysiology: Key Steps

Answer 71

1. Binding & Fusion: HIV attaches to CD4 receptor and a co-receptor (CCR5 or CXCR4) on the host cell surface, then fuses with the cell membrane. 2. Reverse Transcription: Viral enzyme reverse transcriptase converts HIV's RNA genome into double-stranded DNA. 3. Integration: Viral enzyme integrase incorporates the viral DNA into the host cell's DNA. 4. Transcription & Translation: Host cell machinery transcribes viral DNA into mRNA, which is then translated into viral proteins. 5. Assembly & Budding: New viral particles are assembled. Viral enzyme protease cleaves long viral proteins into functional units. New virions bud from the host cell, often destroying it in the process.

Question 72

Acute HIV Infection (Acute Retroviral Syndrome): Clinical Presentation

Answer 72

Occurs typically 2-4 weeks after initial infection (can be up to 28 days). Often mistaken for a mononucleosis-like viral illness. Symptoms: Fever, headache, fatigue, pharyngitis, lymphadenopathy, arthralgias, myalgia, maculopapular rash, GI symptoms. High viral load during this stage. Symptoms usually resolve in a couple of weeks as an immune response develops (seroconversion).

Question 73

Chronic HIV Infection (Clinical Latency): Clinical Presentation

Answer 73

Follows acute infection if untreated. Can last for years (6 months to 10+ years). Often asymptomatic or with mild, non-specific symptoms (e.g., persistent generalized lymphadenopathy). Virus continues to replicate (though at lower levels than acute stage initially), and CD4 cell count gradually declines. Patient remains infectious. Without treatment, progresses to AIDS.

Question 74

Acquired Immunodeficiency Syndrome (AIDS): Definition & Diagnostic Criteria

Answer 74

Definition: The most advanced stage of HIV infection, characterized by severe immune system damage. CDC Diagnostic Criteria for AIDS (in an HIV-infected individual): 1. CD4+ T-lymphocyte count < 200 cells/mm³ OR 2. Presence of any AIDS-defining condition (opportunistic infection or malignancy), regardless of CD4 count.

Question 75

Opportunistic Infections (OIs) in AIDS (General Concept)

Answer 75

Infections caused by pathogens (bacteria, viruses, fungi, parasites) that typically do not cause disease in individuals with healthy immune systems but can cause severe illness in immunocompromised individuals, such as those with AIDS, due to the weakened immune defenses.

Question 76

Candidiasis (Thrush, Esophageal) in AIDS

Answer 76

A common fungal infection caused by *Candida* species. Oral Thrush: White plaques on tongue, palate, or buccal mucosa. Esophageal Candidiasis: Extension into the esophagus, causing dysphagia (painful swallowing), odynophagia. Esophageal candidiasis is an AIDS-defining condition.

Question 77

Cryptosporidiosis in AIDS

Answer 77

A parasitic infection caused by *Cryptosporidium* species, primarily affecting the gastrointestinal tract. In AIDS patients, it can cause severe, chronic, watery diarrhea, leading to dehydration, malabsorption, and weight loss.

Question 78

Cryptococcal Meningitis in AIDS

Answer 78

A life-threatening fungal infection of the membranes covering the brain and spinal cord (meninges), caused by *Cryptococcus neoformans* or *Cryptococcus gattii*. A common opportunistic infection in advanced HIV/AIDS, presenting with headache, fever, neck stiffness, altered mental status. An AIDS-defining condition.

Question 79

Cytomegalovirus (CMV) Disease in AIDS

Answer 79

A viral infection (herpesvirus family) that can cause disseminated disease in severely immunocompromised individuals. CMV Retinitis: Most common CMV manifestation in AIDS, leading to inflammation of the retina, floaters, blurred vision, and potential blindness. An AIDS-defining condition. Other sites: Colitis, esophagitis, pneumonitis, neurological disease.

Question 80

Hepatitis A, B, C in HIV-infected Individuals

Answer 80

Viral infections causing liver inflammation. Co-infection with Hepatitis B (HBV) or Hepatitis C (HCV) is common in HIV-infected individuals due to shared transmission routes (sexual, parenteral). HIV can accelerate the progression of HBV/HCV liver disease. Management is complex. Hepatitis A (HAV) can also occur; vaccination recommended for those at risk.

Question 81

Herpes Simplex Virus (HSV) Infections in AIDS

Answer 81

HSV-1 (oral) and HSV-2 (genital) are common. In AIDS, reactivations can be more frequent, severe, and prolonged. Can cause chronic, ulcerative lesions (lasting >1 month) of the skin, oral mucosa, or genital/perianal area. Chronic mucocutaneous HSV is an AIDS-defining condition.

Question 82

Herpes Zoster (Shingles) in HIV-infected Individuals

Answer 82

Reactivation of Varicella-Zoster Virus (VZV), the virus that causes chickenpox. Presents as a painful, unilateral vesicular rash in a dermatomal distribution. Can be more severe, recurrent, or disseminated in HIV-infected individuals, especially with lower CD4 counts.

Question 83

Human Papillomavirus (HPV) Infections in HIV-infected Individuals

Answer 83

HPV is a common sexually transmitted virus. HIV co-infection increases the risk of persistent HPV infection and HPV-related diseases, including: Anogenital warts. Increased risk and faster progression of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (AIDS-defining). Increased risk of anal, vulvar, vaginal, penile, and oropharyngeal cancers.

Question 84

Kaposi’s Sarcoma (KS)

Answer 84

A vascular tumor (cancer of the endothelium) caused by Human Herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). An AIDS-defining malignancy. Clinical: Red, purple, or brown papules, nodules, or plaques on skin, mucous membranes (oral cavity, GI tract), lymph nodes, and visceral organs (lungs). More common in HIV-infected men who have sex with men.

Question 85

Molluscum Contagiosum in HIV-infected Individuals

Answer 85

A viral skin infection caused by a poxvirus. Characterized by small, firm, umbilicated (dimpled center) papules. In HIV-infected individuals with low CD4 counts, lesions can be more numerous, larger, widespread, and difficult to treat.

Question 86

*Mycobacterium avium* Complex (MAC) Disease in AIDS

Answer 86

An infection caused by non-tuberculous mycobacteria (*M. avium*, *M. intracellulare*). Disseminated MAC disease is common in advanced AIDS (CD4 < 50 cells/mm³). Symptoms: Persistent fever, night sweats, weight loss, fatigue, anemia, abdominal pain, diarrhea, lymphadenopathy. An AIDS-defining condition.

Question 87

*Pneumocystis jirovecii* Pneumonia (PJP)

Answer 87

A fungal pneumonia caused by *Pneumocystis jirovecii* (formerly *P. carinii*). The most common opportunistic infection in AIDS patients before widespread ART and prophylaxis. Symptoms: Progressive dyspnea, non-productive cough, fever, chest discomfort. An AIDS-defining condition. Prophylaxis is given when CD4 counts are low (<200 or <14%).

Question 88

Progressive Multifocal Leukoencephalopathy (PML)

Answer 88

A rare, progressive, demyelinating disease of the central nervous system caused by reactivation of the JC virus (John Cunningham virus). Occurs almost exclusively in severely immunocompromised individuals, such as those with advanced AIDS. Symptoms: Neurological deficits (weakness, cognitive impairment, visual changes, speech problems, ataxia) that worsen over time. Often fatal. An AIDS-defining condition.

Question 89

Toxoplasmosis (Cerebral Toxoplasmosis) in AIDS

Answer 89

A parasitic infection caused by *Toxoplasma gondii*. Reactivation of latent infection is common in AIDS patients with low CD4 counts (typically < 100 cells/mm³). Cerebral toxoplasmosis is the most common presentation, causing multiple ring-enhancing brain lesions. Symptoms: Headache, focal neurological deficits, seizures, fever, altered mental status. An AIDS-defining condition.

Question 90

Tuberculosis (TB) in HIV-infected Individuals

Answer 90

An infectious disease caused by *Mycobacterium tuberculosis*. HIV co-infection significantly increases the risk of latent TB progressing to active TB disease, and active TB can be more severe and atypical. TB is a leading cause of death among people with HIV worldwide. Pulmonary TB is common, but extrapulmonary TB is more frequent in HIV co-infection. Any form of TB (pulmonary or extrapulmonary) in an HIV-infected person is an AIDS-defining condition.

Question 91

AIDS-Defining Malignancies (Other than Kaposi's Sarcoma)

Answer 91

Cancers that occur more frequently or are more aggressive in people with AIDS, and their diagnosis in an HIV-infected person establishes an AIDS diagnosis. Non-Hodgkin’s Lymphoma (NHL): Certain aggressive types, e.g., diffuse large B-cell lymphoma, Burkitt's lymphoma, primary CNS lymphoma. Invasive Cervical Cancer: Caused by HPV, progression is accelerated by HIV.

Question 92

HIV Diagnosis: Laboratory Tests Overview

Answer 92

Screening: HIV antibody/antigen combination assays (4th generation) are recommended. Rapid tests (cheek swab, blood) available. Confirmatory: HIV-1/HIV-2 antibody differentiation immunoassay. Early Detection/Monitoring: HIV RNA assay (viral load) detects virus directly (4-11 days post-infection). Used for diagnosis in acute infection, neonatal diagnosis, and monitoring treatment efficacy. Immune Status: CD4 cell count. CD4:CD8 ratio (inversion from normal 2:1 to 1:2 is characteristic). Drug Resistance: Genotypic resistance testing to guide ART selection. Co-receptor Tropism: To determine suitability for CCR5 antagonists. HLA-B*5701: To screen for abacavir hypersensitivity.

Question 93

Antiretroviral Therapy (ART): Goals & Drug Classes

Answer 93

Goals: Suppress HIV viral load to undetectable levels, restore/preserve immune function (increase CD4 count), reduce HIV-related morbidity and mortality, prevent HIV transmission. Main Drug Classes (mechanisms): Fusion Inhibitors: Block HIV entry. CCR5 Antagonists (Entry Inhibitors): Block HIV binding to CCR5 co-receptor. NRTIs (Nucleoside/tide Reverse Transcriptase Inhibitors): Block reverse transcriptase. NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors): Block reverse transcriptase. INSTIs (Integrase Strand Transfer Inhibitors): Block viral DNA integration. PIs (Protease Inhibitors): Block viral protein processing/maturation. ART usually involves a combination of 3 drugs from at least 2 different classes.

Question 94

HIV Prevention: PrEP & PEP

Answer 94

PrEP (Pre-Exposure Prophylaxis): Daily use of specific antiretroviral drugs (e.g., emtricitabine/tenofovir) by HIV-negative individuals at very high risk to prevent HIV acquisition. Reduces risk significantly if taken consistently. PEP (Post-Exposure Prophylaxis): Use of antiretroviral drugs for 28 days after a single high-risk event (occupational or non-occupational exposure) to prevent HIV infection. Must be started within 72 hours of exposure.

Question 95

Immune Reconstitution Inflammatory Syndrome (IRIS)

Answer 95

A condition seen in some HIV-infected individuals after starting or changing ART. As the immune system recovers (CD4 count increases), it may mount an exaggerated inflammatory response to pre-existing (often subclinical) opportunistic infections or antigens. Hallmark: Paradoxical worsening of an existing infection/disease or appearance of a new one despite virological suppression. Commonly associated with mycobacterial infections (TB, MAC), fungal infections (cryptococcus), CMV, herpes viruses.