SEARCH RESULTS FOR: pharyngitis

Group A Streptococci Pharyngitis Pathogenesis and Clinical Findings

Scarlet Fever: Pathogenesis and clinical findings

Scarlet Fever: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Note: GAS pharyngitis can be left untreated, but scarlet fever MUST be treated. Enters systemic circulation Delayed type hypersensitivity response See slide on Type IV Hypersensitivity: Pathogenesis and Clinical Findings Abbreviations: GAS – Group A Streptococci SPE – Streptococcal Pyogenic Exotoxin SSA – Streptococcal Superantigen Group A Streptococci Infection1 5-15 years old2 Adhesins, including lipoteichoic acid and M protein, within GAS cell wall facilitates regional adherence to pharyngeal epithelial cells GAS releases SPE A, B and C, and SSA Stimulation of T-cells and mononuclear cells General inflammatory response White strawberry tongue3 Coating sluffs off after 2-3 days Red strawberry tongue4 Complications: See slide on Group A Streptococci Pharyngitis: Pathogenesis and Clinical Findings Scarlatiniform rash (sandpaper feel) 0-1 days post- pharyngitis Pastia’s lines5 1-2 days post- pharyngitis Appears on upper trunk and axillae 3-4 days post- pharyngitis Spreads to remainder of body, sparring face6, palms and soles 7-10 days post- pharyngitis Fades Desquamation7 Otitis media, sinusitis, pneumonia, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, and acute rheumatic fever Fine maculopapular rash Blanchable with Non-pruritic and pressure painless Notes: 1. While the majority of infections are cases of GAS pharyngitis, rarely, it is possible to develop scarlet fever from a GAS skin infections. 2. Scarlet fever is most common in patients of this age group although, rarely, it can occur in adults. 3. White strawberry tongue is characterized by a white coating on the tongue through which edematous lingual papillae project. 4. Red strawberry tongue is characterized by a beefy red, edematous tongue covered in edematous lingual papillae. 5. Prominent erythema and petechiae in the body folds, especially the antecubital fossae and axillary folds. They tend to appear before the rash and persist through the desquamation phase. 6. Typically, the rash does not occur on the face, although facial flushing may be noted. When this occurs, there is perioral sparring. 7. Desquamation tends to occur ~1 week after the rash fades, most severely effecting the hands and feet, and lasts 2-6 weeks. While a classical presentation, not everyone gets it. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Sinusitis: Pathogenesis and clinical findings

Sinusitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Abbreviations URTI – Upper respiratory tract infection Nasal obstruction/ congestion Hyposmia Headache Facial pain/pressure Maxillary tooth pain Ear pain/ fullness Osteomyelitis of frontal bone Chemical irritants Cystic Fibrosis Direct toxic effect on cilia Viral URTI Allergies Inflammation of paranasal sinuses Edematous passageways Septal deviation Adenoid hypertrophy Polyps Turbinate hypertrophy Tumors Foreign body Dysfunctional cilia Congenital and/or craniofacial abnormality Obstruct sinus ostia Cilia unable to clear mucus from sinuses Mucus unable to drain through ostia Post-nasal drip Mucus overflows from the sinuses Cough Mucus accumulates in sinuses Occupies a larger volume Applies ↑ pressure to sinus walls Mucopurulent discharge Bacterial1 overgrowth in sinuses Bacterial infection spreads to adjacent structures Halitosis Pharyngitis Throat clearing Dental root infection Immunodeficiency Note: Irritates the back of the throat Perforation of the Schneiderian membrane2 Passage of bacteria into the sinuses Fever Fatigue Subperiosteal orbital abscess Orbital abscess Orbital edema ↑ susceptibility to bacteria 1. The most common bacteria are Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis. Staphylococcus aureus and Group A Streptococcus may be seen, but are less common. However, in cases of dental root infection, oral anaerobes become more common, while Pseudomonas species are associated with foreign bodies. 2. The Schneiderian membrane is the membranous lining of the maxillary cavity. Cavernous sinus thrombosis Meningitis Cerebral abscess Subdural abscess Epidural abscess Periorbital or orbital cellulitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Erythema Nodosum pathogenesis and clinical findings

Erythema Nodosum: Pathogenesis and clinical findings Authors: Merna Adly Reviewers: Taylor Evart Woo Crystal Liu Yan Yu* Laurie Parsons* * MD at time of publication Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous Fat Layer Phase 1-5. Septal Fibrosis made of inflammatory cells, such as T lymphocytes, histocytes and eosinophils Genetic Dysregulation Infections (Ex. Streptococcal Pharyngitis) ~28-48% of cases Medications (Ex. Birth Control Pills, Sulfa drugs) ~3-10% of cases Malignancy (ex. Lymphoma) Autoimmune conditions (ex. Sarcoidosis and Inflammatory Bowel Disease) ~11-25% of cases Pregnancy ~1-3% of cases Antigenic Stimuli / Bacteria / Viruses / Chemical Agents all could trigger the following process: Phase 1. Neutrophils Infiltrate the fibrous septa between fat lobules in the subcutaneous fat Phase 2. Neutrophils release reactive oxygen species, leading to oxidative tissue damage and inflammation Phase 3. Opening of inter-endothelial junction and the migration of more inflammatory cells into the septal venules, including macrophages, histocytes, and eosinophils Phase 4. Macrophages secrete inflammatory cytokines, which stimulates the proliferation of more helper T cells (Th1) Phase 5. Th1 cells secrete more cytokines, leading to the further release of Th1 cytokines and mediating the immune complexes deposition in the septal venules of the subcutaneous fat (panniculitis). The Th1 immune reaction is called Type IV Delayed Hypersensitivity Reaction Phase 6. Activated macrophages produce hydrolytic enzymes and transform into multi- nucleated giant cells, called Miescher’s Radial Granulomas. These consist of small, well defined aggregations of small histocytes arranged radially around a small cleft of variable shapes in the septal venules of the subcutaneous fat Phase 1-4. Lesions are red tender nodules, poorly defined, vary in size from 2-6 cm, and usually on shins ( 1st week) Fat Lobules T lymphocytes Macrophages Note: we’ve done extensive research and can’t figure out why erythema nodosum happens mostly on the shins. If you have an answer, please email us! Phase 5. Lesions become tense, hard, and painful; and they change in color into bluish or livid. (2nd week) Phase 6. Lesions become fluctuant as in abscess, but do not ulcerate. Lesions fade to a yellowish color Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous Fat Layer Phase 6. Miescher’s Radial Granulomas Fat Lobules T lymphocytes Macrophages Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 25, 2019 on www.thecalgaryguide.com

necrotizing fasciitis

Necrotizing Fasciitis: Pathogenesis and Clinical Findings Authors: Alyssa Federico, Amanda Eslinger, Matthew Harding, Mehul Gupta Reviewers: Heena Singh, Yan Yu*, Donald Graham*, Duncan Nickerson* * MD at time of publication Diabetes Loss of protective sensation in lower extremities Peripheral vascular disease Poor arterial perfusion causes necrosis of tissue Immune compromised host Increased susceptibility to infection Bacteria introduced to tissue Pharyngitis Blood carries bacteria from throat to other tissue (hematogenous spread) Laceration Recent surgery Injection Burn Blunt force trauma Childbirth Lower extremity wounds Bacteria enters tissue through open wound Infection of muscle fascia Local immune response Production of exotoxins by bacteria Disruptions of protective skin barrier Bacteria introduced into tissue during injury Necrotizing Fasciitis Type I infection: mixed aerobic and anaerobic bacteria Type II infection: group A streptococcus Type III infection: marine organisms, clostridial infections Type IV infection: fungal organisms Poor blood supply of muscle fascia allows for progressive spread of infection Systemic immune response Pyrogens produced by immune system Pyrogens travel through the bloodstream to the hypothalamus and alters the body’s thermal setpoint Transmission of bacteria from infected tissue to blood Sepsis Streptolysin (exotoxin) causes blood clot formation Blood clots in vessels Tissue ischemia in epidermis, dermis, subcutaneous fat, muscle fascia, and/or muscle Stimulation of programmed cell death Tissue destruction Pain more severe than clinical findings ↓ blood flow fails to meet tissue’s needs Tissue death Build up of gas in subcutaneous tissue from bacteria metabolism Crepitus ↑ serum creatinine kinase from protein breakdown ↑ blood flow to infected tissue Warmth Erythema Immune cells release vasoactive cytokines into the blood Capillary vasodilation Fluid and proteins shift from cells and capillaries to interstitial space Blood vessel dilation ↓ perfusion of vital organs Organ failure Hypotension ↑ heart rate to perfuse vital organs Tachycardia Bacteria releases toxins which are taken up into the bloodstream Immune cells produce inflammatory cytokines Circulating toxins activate T cells, over- activating the systemic immune response Toxic Shock syndrome Infection ↑ white blood cell production in bone marrow ↑ white blood cells Destructionof peripheral nerve endings Insensitivity to pain Tissue hypoxia à anaerobic metabolism Poor perfusion of lungs impairs gas exchange Tachypnea Cytokines affect dopamine production in the basal ganglia Acute malaise Production of non-specific acute phase reactants ↑ C reactive protein and erythrocyte sedimentation rate Fluid-filled blisters Edema Fever Compartment syndrome (see relevant Calgary Guide slide) Amputation ↑ serum lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Nov 20, 2013, updated Dec 19, 2021 on www.thecalgaryguide.com

IgA Nephropathy

IgA Nephropathy: Pathogenesis & clinical findings Authors: David Campbell Matthew Hobart Reviewers: Huneza Nadeem Raafi Ali Ran Zhang Luiza Radu Julian Midgley* * MD at time of publication Galactose-deficient IgA1 (GD- IgA1) created by mucosa- bound IgA1 plasma cells is secreted into plasma instead of onto mucosal surface IgA1 plasma cells hyper- responsive to triggers (eg. URTIs, gastroenteritis) ↑ synthesis of GD-IgA1 → spill-over into plasma Immunoglobulin A1 (IgA1) plasma cells destined to reside in mucosa (eg. gut or respiratory tract) travel to and reside in inappropriate site(s) (eg. bone marrow) releasing GD-IgA1 into plasma GD-IgA1 is not cleared from plasma as quickly as IgA1 → ↑ plasma GD-IgA1 levels Hit 3: GD-IgA1-IgG complexes deposit in mesangium C3 predominant complement activation amplifies inflammatory response Renal biopsy: IgA deposits in mesangium (100% sensitive) Renal biopsy: Complement in mesangium (C3 predominant) (90-95% sensitive) A cascade of multiple immunologic hits is initiated Hit 1: ↑ Serum levels of GD-IgA1 multiple immunologic hits GD-IgA1 hinge region is structurally distinct from IgA1 that would normally circulate in plasma (lack of galactosyl groups) GD-IgA1 hinge region may mimic pathogens (ex. bacteria and viruses) or other antigens Cross reactivity of IgG against GD-IgA1, or synthesis of anti-GD-IgA1 IgG antibodies Immunoglobulin G (IgG) binds GD-IgA1 hinge region Hit 2: GD-IgA1-IgG immune complex formation Circulating GD-IgA1-IgG complexes have high affinity for glomerular endothelial cells where they damage the glycocalyx → ↑ permeability of immunoglobulins into the mesangium ↑ Production of chemokines, cytokines and complement → ↑ mesangial cell proliferation and matrix expansion Leukocyte recruitment and activation damages glomerulus and mesangium Hit 4: Inflammatory response to GD-IgA1 complexes in mesangium induce glomerular structure disruption (endothelium, basement membrane, podocytes, mesangium) and impaired glomerular function Loss of barrier functions of glomerulus allows for extravasation of blood & proteins into Bowman’s space and subsequently through tubules Renal biopsy: Glomerulosclerosis, tubulointerstitial fibrosis, glomerular vasculitis, podocyte damage Eventual end-Stage Renal Disease (ESRD) Progressive ↓ of filtration surface area within glomeruli and ↓ number of functional glomeruli Proteinuria Synpharyngitic hematuria (hematuria with dysmorphic red cells co-occurring with pharyngitis) ↓ Glomerular Filtration Rate (GFR) Nephrotic Syndrome ↑ Serum creatinine Chronic kidney disease and eventually ESRD IgAN is an autoimmune disease where IgA deposition in the glomerulus leads to an inflammatory cascade, endothelial dysfunction and mesangial expansion that damages glomeruli causing kidneys to leak blood and protein into urine and decreased kidney function. IgA nephropathy is a multifactorial disease requiring multiple immunologic hits IgA Nephropathy (IgAN) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 5, 2024 on www.thecalgaryguide.com

Tonsillitis Pathogenesis and clinical findings

Tonsillitis: Pathogenesis and clinical findings Authors: Taylor Krawec Amanda Marchak Reviewers: Nicola Adderley, Jim Rogers Emily J. Doucette, Danielle Nelson* James D. Kellner* * MD at time of publication Pathogen infiltrates tonsillar epithelium Microfold cells recognize pathogen & activate immune response Virus (most common) Group A Streptococci (GAS) (most common bacteria) Group B, C & G Strep, Fusobacterium necrophorum Age 5-15 (tonsils have ↑ role in immune function at this age) Tonsillitis Inflammation of the tonsils Infectious agent exposure Susceptible host Pathogen colonizes the oropharynx Acute suppurative disease Immune cells release proinflammatory cytokines & antibodies Inflammatory mediators ↑ vascular permeability of tonsils Leakage of protein & fluid into surrounding tissue Regional nodes receive ↑ lymph Enlarged anterior cervical nodes Sinusitis** Pharyngitis** Local spread of pathogen Acute otitis media** Pneumonia** Cervical lymphadenitis Bacteria spread from tonsils into lymphatic system & bloodstream Bacteremia F. necrophorum invades lateral pharyngeal space & soft tissue in neck Thrombosis forms in peritonsillar vein Thrombosis extends into internal jugular vein Lemierre’s syndrome Systemic inflammatory cytokines disrupt hypothalamic regulation Fever Additional immune cells are recruited to facilitate immune response Macrophages phagocytize pathogen Bacteria invade distant tissue & elicit local inflammatory response Hepatitis Osteomyelitis Infective endocarditis Bacteria illicit systemic response Sepsis Tonsillar tissue become swollen & irritated Tonsillar hypertrophy Localized collection of pus forms Immune cells cause inadvertent cellular injury & hemolysis Palatal petechiae Meningitis Products of immune response & cellular debris are deposited into tonsillar tissue Peritonsillar or Tonsillar retropharyngeal abscess** exudate ** See corresponding Calgary Guide slide Toxin-mediated disease Bacteria release exotoxins into bloodstream Inflammatory mediators & cytokines are overactivated (cytokine storm) Skin has local inflammatory response Toxic shock syndrome** Scarlet fever** Post-infectious disease Antibodies to GAS cross react with host tissue Acute rheumatic fever** Post-strep glomerulonephritis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 5, 2018; updated Mar 14, 2025 on www.thecalgaryguide.com

Acute Infectious Mononucleosis

**See corresponding Calgary Guide slides Legend: Acute Infectious Mononucleosis: Pathogenesis & clinical findings Viral transmission (Epstein-Barr virus (EBV), Cytomegalovirus (CMV), human immunodeficiency virus (HIV), etc) through saliva (most commonly in adolescents & young adults aged 15-24) Virus infects epithelial cells of the oropharynx Virus infects & immortalizes circulating B lymphocytes Virus replicates in infected B-cells Immune cell proliferation in lymphatic system (primarily lymph nodes & spleen) Infected B-cells enter systemic circulation Systemic inflammatory response activated Inflammation & edema of sinuses Bilateral periorbital &/or palpebral edema Pharyngitis** (often with grey/white exudative secretions) Palatal petechiae Blood vessel damage in the soft palate Edema of soft palate & tonsils Airway obstruction ↑ Immunoglobulin M (IgM) antibodies to EBV viral capsid antigen (VCA) Positive IgM-VCA Immortalized B-cells produce ↑ antibodies Production of heterophile antibodies (weakly reactive & non-specific) Positive monospot (heterophile antibody) test (↓ sensitivity in children <4 years) Virus may remain dormant in B-cells Latent infection with periodic reactivation Generalized lymphadenopathy (enlarged lymph nodes) Massive cervical, mediastinal or hilar lymphadenopathy Posterior cervical lymphadenopathy Platelets sequestered (trapped) within spleen & overactive spleen (hypersplenism) discards ↑ platelets Thrombocytopenia (↓ platelets) Weak reticular tissue in the spleen stretches Splenomegaly Splenic rupture & becomes more susceptible to injury Inflammatory response ↑ energy demand Fatigue Longstanding impacts from unknown mechanism Chronic Fatigue Syndrome Inflammatory cytokines released into circulation ↑ Thermo-regulatory set-point at hypothalamus Fever Lymphocytosis (↑ lymphocytes) (markedly CD8+ T-cells & NK cells) Immune cells infiltrate the liver Hepatomegaly ↑ Aminotransferases Leukocytosis (↑ leukocytes) CD8+ T-cells & NK cells indirectly damage hepatocytes ↑ Bilirubin & jaundice** Systemic immune response &/or antibiotic hypersensitivity reaction CD8+ T-cells respond to virus Atypical lymphocytes on blood smear Generalized maculopapular rash Authors: Ayden Hansen, Griselle Leon Reviewers: Charissa Chen, Emily J. Doucette Danielle Nelson* * MD at time of publication Published Sept 3, 2015; updated Apr 22, 2025 on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications

Infection-Related Glomerulonephritis

Infection-Related Glomerulonephritis: Pathogenesis & clinical findings Viral or bacterial infections (most commonly streptococcus & staphylococcus) trigger the inflammatory cascade Common infection sites include pharyngitis (infection of the mucous membranes in the oropharynx) & endocarditis (inflammation of the endocardium) but bacterial infections can originate anywhere in the body In streptococcal infections, bacteria release nephritis (inflammation of the kidney) associated plasmin receptor antigens (NAPlr) & streptococcal pyrogenic exotoxin B antigens (SPeB) into the systemic circulation from the infection site. Other bacterial infections may have different pathophysiology Immune response generated against circulating NAPlr & SPeB antigens includes ↑ production of IgG antibodies (critical for immune response & memory) IgG antibodies bind with self-antigens (molecules recognized by the immune system as belonging to the host) including plasmin & glomerular proteins (proteins found in the kidney’s filtering unit, the glomerulus) IgG antibodies activate plasmin (enzyme responsible for breaking down protein in the kidneys) Plasmin degrades protein in the kidneys IgG antibodies bind to glomerular proteins in the kidney & form immune complexes in glomeruli basement membrane & sub- epithelial podocytes (highly specialized cells in the glomerular filtration barrier) Degradation of key glomerulus components, including the glomerular basement membrane (GBM) & mesangial matrix Damage to key glomerulus components leads to abnormal regulation of blood filtration ↓ Selective permeability of the glomerular membrane IgG antibodies bind with NAPIr & SPeB antigens & form immune complexes (antibody & antigen combinations involved in immune system signalling) Immune complexes circulate & deposit in glomeruli basement membrane & sub-epithelial podocytes RBCs escape through the glomerulus into renal tubules & progress into the urine Dysmorphic hematuria (blood in the urine characterized by misshapen RBCs) Author: Joanna Keough Reviewers: Britney Wong Luiza Radu Jessica Revington Veronica Hammer* Louis Girard* *MD at time of publication **See corresponding Calgary Guide slide Legend: Pathophysiology Mechanism Immune complexes activate complement (C3, oxidizing agents, proteases) Complement activation helps ↑ proliferation of glomerular mesangial cells (cells with specialized proteins capable of producing motile forces) Mesangial cells produce extracellular matrix in the glomerulus Excess extracellular matrix blocks glomerular capillaries Mesangial cells release chemoattractants (signalling molecules) into the glomerulus & attract various immune cells Lymphocytes follow chemoattractants to the glomerulus & activate Neutrophils follow chemoattractants to the glomerulus & release lysosomal enzymes Lymphocytes accumulate in the glomerulus & obstruct glomerular capillaries Impaired blood flow through glomerular capillaries Capillary injury Podocyte injury or death Infection-Related Glomerulonephritis Glomerular kidney damage sustained after a bacterial or viral infection ↓ Glomerular filtration rate (GFR) Creatinine builds up in the blood ↑ Glomerular membrane permeability allows large molecules to pass through the membrane (e.g., red blood cells (RBCs), protein) ↓ GFR impairs the kidney’s ability to filter & excrete fluid ↓ Estimated GFR Prolonged (eGFR) renal damage Protein escapes into renal tubules & progresses into the urine Chronic kidney disease Proteinuria (loss of protein through the urine) ↑ Fluid retention in systemic circulation & ↓ renal blood flow Impaired potassium excretion ↓ Urine output Impaired acid waste product excretion Urine contains ↑ large proteins (e.g., albumin) Activation of the intrarenal renin- angiotensin-aldosterone system (RAAS)** Hyperkalemia (↑ serum potassium) Oliguria (↓ urine volume) Metabolic acidosis** Albuminuria (loss of albumin through the urine) Intrarenal RAAS activation leads to ↑ angiotensin II (Ang II) production ↑ Sodium & water retention in systemic circulation & ↓ excretion in urine (↓ GFR) Hypertension** Edema (swelling due to ↑ fluid in body tissues) Circulating blood volume exerts ↑ pressure on blood vessels & forces the heart to pump harder Left ventricle thickens & enlarges over time & demonstrates progressive cardiac injury (e.g., fibrosis, loss of cardiac muscle cells) Impaired cardiac output Heart failure Sign/Symptom/Lab Finding Complications Published November 15, 2025 on www.thecalgaryguide.com