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

Tonsillitis: Pathogenesis and clinical findings

Tonsillitis: Pathogenesis and clinical findings Group A Streptococci (GAS) infection1,2 Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Viral pathogen1 5-15 years3 Pathogen colonizes the nasopharynx Pathogen colonizes oropharynx4 ** ↑ vascular permeability Leakage of protein and fluid into surrounding tissue Inflammatory cytokine release Inadvertent cellular injury and hemolysis Tonsillar petechiae and erythema Systemic inflammatory cytokines disrupt hypothalamic regulation Fever White blood cell (WBC) activation WBCs infiltrate site of infection WBCs kill pathogen Accumulation and deposition of cellular debris and products of inflammatory response Tonsillar exudate Note: *When GAS is the pathogen, cytokine release and WBC activation is secondary to the release of exotoxins by GAS. Swelling and irritation ↑ lymph drainage to regional nodes Enlarged anterior cervical nodes Cough Note: It is extremely important to distinguish between viral tonsillitis and bacterial tonsillitis. Viral tonsillitis is usually self-limited while GAS tonsillitis can be associated with a number of complications. Notes: Tonsillar tissue Tonsillar edema Nasal tissue6 Nasal congestion Coryza Nasal discharge irritates back of throat Complications5: Peritonsillar abscess, neck abscess, otitis media, sinusitis, pneumonia, scarlet fever, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, acute rheumatic fever, and toxic shock syndrome 1. In general, viral tonsillitis is more common than GAS infection. However, in the absence of cough and coryza (acute, isolated tonsillitis), GAS is more common. 2. While GAS is the most bacterial cause of tonsillitis, it can be caused by other pathogens. 3. GAS tonsillitis is most common in patients of this age group although, rarely, it can occur in adults. 4. When GAS colonizes the oropharynx, the primary location of infection determines how it’s identified. • tonsils primarily effected = tonsillitis • pharynx (throat) primarily effected = pharyngitis (See slide on Group A Streptococci Pharyngitis: Pathogenesis and Clinical Findings) • both = pharyngotonsillitis 5. The listed complications are the result of exotoxins entering systemic circulation or the bacterial infection extending beyond the tonsils. 6. While viral tonsillitis tends to be associated with more upper respiratory tract symptoms, clinical signs and symptoms are NOT reliable for diagnosing GAS tonsillitis. Throat swab or rapid antigen detection test are the standards for diagnosis. 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