Module 10 Flashcards
List some allergic type disorders
Atopic dermatitis
allergic rhinitis
otitis media
lung cancer
increased respiratory infections
Auto-immune type diseases
Thyroiditis
Celiac disease
MS
Sleep problems
Hearing loss
Depression
Atherosclerosis
Inflammation related disease patterns
Colorectal cancer
Depression
Rheumatoid arthritis
MS
Autoimmune hepatitis
Asthma
Paediatric deep vein thrombosis
AS
Infection related disease patterns
Otitis media
Asthma
chronic bronchitis
Atherosclerosis
Lung cancer
Adult snoring
secondary bacterial infections
Food allergies
what’s the incidence in Australia
- Threefold rise in the prevalence of peanut and tree nut allergy between 1997 and 2008
- Australia has one of the highest rates of food allergies in the world
- IgE mediated food allergy affects up to 10% of 12 month old infants 9% egg allergic
3% peanut allergic
27% affected by eczema
What is driving the food allergy epidemic?
- Decliningmicrobialexposure–bothbeneficialand pathogenic
- Pro-inflammatorywesterndiet
- Inhaled pollutants–ca rtraffic, cigarette smoke
- Genetic and epigenetic factors
- Increased incidence if born during autumn or winter
- Maternal VitD and EFAs intake
- Caesarian delivery
The development of the immune system in children
Describe the Th1/Th2 balance for a healthy immune system.
Youtube for good explanation I reckon
https://youtu.be/n8s7nDqLucA
Good explanation on this YouTube video
Th1/ Th2 Balance = healthy immune system
What does each of them do in the immune system?
Th1: Cell mediated inflammation and delayed -type hypersensitivity reactions
Immunity to intracellular pathogens
Produce IL2 and IFN-y
Defenence against:
-Virus
-Bacteria
-Fungi
-Tumours
Th2:
Mainly function in epithelial cells
-lungs
-GI tract
Produce IL-4, IL-5 and IL-13
defence against:
Allergens
-Chemicals
-Parasites
Th17 Cells and Th22 Cells
What do each of them do
What if there is an increase in IL17?
Th17:
The IL-17 family of cytokines comprises potent inflammatory mediators involved in host defense against extracellular bacteria, fungi and other eukaryotic pathogens
* IL-17 cytokines have been implicated in a broad spectrum of inflammatory conditions and autoimmune diseases
* IL-23 promoted the generation of IL-17 producing Th cells
Th22:
* Produce cytokine IL-22
* associated with immunopathology of skin
diseases
* IL-22 plays an important role in the pathogenesis of autoimmune diseases including psoriasis, SLE, MS, RA, and allergic diseases, thereby implicating Th22 cells and IL-22 as a potential therapeutic target in autoimmune diseases
Th1 Excess disorders list
Tissue specific auto-immune disorders
1. Rheumatoid arthritis
2. Multiple sclerosis
3. Type 1 diabetes mellitis
4. Psoriasis
5. Crohn’s disease
6. Sarcoidosis
Sarcoidosis is a disease characterized by the growth of tiny collections of inflammatory cells (granulomas) in any part of your body — most commonly the lungs and lymph nodes. But it can also affect the eyes, skin, heart and other organs.
- Hashimoto’s thyroiditis
- Unexplained recurrent miscarriage
- Predisposes to parasitic infections
Th2 Excess disorders list
- Allergies
- Infections
- Asthma
- Eczema
- Graves disease
- Irritable bowel syndrome
- Ulcerative colitis
- SLE
- Scleroderma
- Chronic Fatigue Syndrome
What disrupts the Th1/Th2 balance?
The gut microbiota shapes intestinal immune responses during health and disease
Instead this could be due the effects of antimicrobial strategies:
????????
Sanitation
Western diet antibiotic
Antibiotics and chronic ill health
Use of broad spectrum anti-biotics in the first six months of life was associated in an 8.9 times increased risk of developing asthma.
Early anti-biotic use may influence the gastrointestinal tract and alter the development of the maturing immune system.
Why Th2 dominance in infants?
- PregnantmotherisTh2dominanttoprotectthe foetus from immune mediated rejection
- Babies are born in aTh2 dominant state
- The immune system consists essentially of the innate immune system and the adaptive immune system.
- The innate immune system is the sum of physical barriers, chemical barriers, and the reactivity of local nonspecific cells and cells recruited to the site of inflammation.
- The innate non specific immune system is not fully developed or active in first year of life.
- Theadaptiveimmunesystem
The most widely recognised component is sIgA - The fetal immune system is particularly vulnerable to disruptions caused by environmental factors that have an impact on the maternal immune system, such as malnutrition, toxins and stress
- The foetus receives transplacental maternal IgG
Small amounts are transferred early in gestation with rapid increase
in transfer after 20 weeks
remaining intact in the infant up to the age of 3–6 months - Food- derived antigens are transferred through the placenta into the amniotic fluid and cause prenatal formation of antigen-specific IgE antibodies
- Antigen specific responses to rubella and helminth parasites have been recorded in the second trimester
- Prenatal infections have been linked to Schizophrenia
Autism
Mental retardation
Maternal exposure to stress
what has research shown us?
- Infants whose mothers were characterized as anxious in pregnancy exhibited poorer adaptive immune response at 6months of
age.
reduced hepatitis B antibody titers following immunization(in vivo),
increased IL-4 and decreased IFN-γ responder cell frequencies to antigen(in vitro). - This implies that there is a reduced type 1 and increased type 2 response in the infant
maternal prenatal anxiety exaggerates the normal type 2 skewing and less robust type 1 cytokine response to specific antigens - IgE levels in the infant at birth were predicted by chronic stress as reported by mothers
What are factors that negatively influence/ impact gut flora
- caesareansection
There is growing evidence that caesarian section is associated with poor immunological development (Battersby and Gibbons) - formula-baseddiet
- Use of antacids
- hygiene
- ?????????
- use of antimicrobials in infants(antibiotics)
- Environmental chemicals: pesticides, insecticides, pollutants, cleaning agents, BPA (plasticisers), heavy metals etc.
Neonates and formula feeding
- Recent reports associate artificial feeding of neonates with subsequent chronic diseases of later life, especially those with an autoimmune component
- Theincreasednumberofprematureinfantsin neonatal intensive care units has been accompanied by an epidemic of inflammatory bowel diseases, especially necrotizing enterocolitis (NEC)
Ninety percent of NEC patients had been fed formula without human milk and inclusion of human milk in the diet of the premature infant is associated with a lower risk of NEC.
Human milk accelerates maturation of the gut barrier function, but formula does not
neonate is protected from pathogenic insults during this vulnerable period by bioactive components of human milk, primarily sIgA, and products of an innate immune system of human milk - Breast-fedinfantshaveapredominanceoflactobacilli, especially Lactobacillus bifidus (now Bifidobacterium bifidum), thought to acidify the gut and inhibit enteric pathogens from infecting breast-fed infants
- Lactoferrin
Is a major protein of human milk that chelates free iron,
potentially assisting iron absorption by the infant.
Unbound iron is an essential nutrient for many bacteria, and by making it unavailable, lactoferrin would also have a broad bacteriostatic effect
Partial digestion of lactoferrin produces lactoferricin B, a positively charged peptide loop of 18 amino acids with potent broad antibacterial activity for both Gram-positive and Gram-negative bacterial pathogens.
Lactoferrin also inhibits pathobiology of several bacteria, stimulates phagocytosis of pathogens by macrophages, and inhibits human immunodeficiency virus, cytomegalovirus, and herpesvirus. - Human milk contains more than 109 leukocytes per litre for the first several months of lactation
The immunological memory of the mother is passed to her infant via breast milk
- Improperimmunematurationmayleadtolifetime immunological disorders such as allergic disorders and autoimmunity.
- Theinteractionbetweenmotherandchildpostpartum plays an important role in the development of the infant’s immune system.
- Theimmunologicalmemoryofthemotherispassed to her infant via breast milk
Neonates and formula feeding
- Recent reports associate artificial feeding of neonates with subsequent chronic diseases of later life, especially those with an autoimmune component
- Theincreasednumberofprematureinfantsin neonatal intensive care units has been accompanied by an epidemic of inflammatory bowel diseases, especially necrotizing enterocolitis (NEC)
Ninety percent of NEC patients had been fed formula without human milk and inclusion of human milk in the diet of the premature infant is associated with a lower risk of NEC.
Human milk accelerates maturation of the gut barrier function, but formula does not
neonate is protected from pathogenic insults during this vulnerable period by bioactive components of human milk, primarily sIgA, and products of an innate immune system of human milk - Breast-fedinfantshaveapredominanceoflactobacilli, especially Lactobacillus bifidus (now Bifidobacterium bifidum), thought to acidify the gut and inhibit enteric pathogens from infecting breast-fed infants
- Lactoferrin
Is a major protein of human milk that chelates free iron,
potentially assisting iron absorption by the infant.
Unbound iron is an essential nutrient for many bacteria, and by making it unavailable, lactoferrin would also have a broad bacteriostatic effect
Partial digestion of lactoferrin produces lactoferricin B, a positively charged peptide loop of 18 amino acids with potent broad antibacterial activity for both Gram-positive and Gram-negative bacterial pathogens.
Lactoferrin also inhibits pathobiology of several bacteria, stimulates phagocytosis of pathogens by macrophages, and inhibits human immunodeficiency virus, cytomegalovirus, and herpesvirus. - Human milk contains more than 109 leukocytes per litre for the first several months of lactation
The immunological memory of the mother is passed to her infant via breast milk
- Improperimmunematurationmayleadtolifetime immunological disorders such as allergic disorders and autoimmunity.
- Theinteractionbetweenmotherandchildpostpartum plays an important role in the development of the infant’s immune system.
- Theimmunologicalmemoryofthemotherispassed to her infant via breast milk
What does breastfeeding reduce incidence off?
Innate immune system of human milk
*
Breastfeeding reduces the incidence of
Gastrointestinal infections Respiratory tract infections Otitis media
SIDS
Type 1 and type 2 diabetes Atopic dermatitis
Asthma
Obesity
NEC
(Chung et al 2009)
Promoting effect of long term breastfeeding on food allergies disappears once confounding factors are excluded (except possibly with gluten)
- Formula fed infants
have a three to ten fold higher risk of disease,
especially enteric infection leading to diarrhoea
Increased chronic disease in later life
Increased autoimmune disease
Have a much smaller thymus gland
what is the role of the microbiome in central nervous system d
CNS effects of probiotics
- Bifidobacerium infantis has been shown to have antidepressant action
- In a ground breaking functional magnetic resonance imaging (fMRI) brain scan study Tillisch et al. (2013) showed that ingestion of a probiotic cocktail altered information processing of emotional material.
Probiotics
Modulate endogenous flora of the GI tract
- Modulate endogenous flora of the GI tract
- Reduce intestinal permeability
- Augment cellular and humoral immunity
- Modulate systemic intestinal allergy and inflammation
Reduce intestinal permeability
Bifidobacterium restores tight junction proteins
Augment cellular and humoral immunity
Stimulate phagocytic function of macrophages, natural killer cells, monocytes and neutrophils.
IgA response to rotavirus is enhanced by lactobacillus
Modulate systemic intestinal allergy and inflammation
Up regulate anti-inflammatory cytokines (e.g. interleukin 10) Increase Regulatory T cell function
What are the effects of early prebiotic and probiotic supplementation on development of Gut Microbe and fussing and crying in preterm infants
Conclusion in huge high quality study said early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants.
The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics. The prevention of atopic eczema in high-risk infants is possible by modulating the infant’s gut microbiota with probiotics and prebiotics.
Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life
These data suggest that probiotics may offer a safe means of reducing the risk of early acute otitis media and antibiotic use and the risk of recurrent respiratory infections during the first year of life
Daily dietary probiotic supplementation for 6 months was a safe effective way to reduce fever, rhinorrhea, and cough incidence and duration and antibiotic prescription incidence, as well as the number of missed school days attributable to illness, for children 3 to 5 years of age
Management of immune system imbalance in infants and children
Treatment of Th2 excess
- Luteolin (Metagenics – Luteol Plus or Allergese)
1. Found in chinese herb Perilla frutescens
2. Inhibits production of Th2 cytokines
3. Inhibits release of histamine - Quercetin
1. Inhibits production of Th2 cytokines
2. Inhibits release of histamine
3. Anti-inflammatory - Probiotics
- D3
1. Prevents Th2 driven development of asthma
Note: Astragalus
1. Enhances both TH1 and Th2 responses
Paediatric Dermatology
Types of skin lesions
- SystemicLE(SLE)is a chronic inflammatory multi system disease.
- It is a diagnosed when 4 of 11 well- defined criteria are present.
- Three of the criteria are skin findings.
Criterion 1 is the classic malar or “butterfly” rash
It must be distinguished from other causes of a “red face,” most notably seborrheic dermatitis, atopic dermatitis, and rosacea.
Criterion 2 is a discoid rash.
Criterion 3 is a photosensitive erythematous macular or papular
eruption. - Other associated but not diagnostic cutaneous findings include purpuric lesions, livedo reticularis, mucosal ulcerations, Raynaud phenomenon, and nonscarring alopecia.
Vasculitides are a heterogeneous group of autoimmune diseases, all characterized by inflammation of blood vessels (vasculitis) and subsequent ischemia and damage to the organs supplied by these vessels. Vasculitis may occur as a primary disease (idiopathic) or as a secondary response to an underlying disease (e.g., hepatitis B infection
).
- Henoch-SchönleinPurpura(IgA Vasculitis)
manifests as purpuric lesions prominently on the buttocks and lower extremities of school-aged children - KawasakiDisease
manifesting variously as urticarial, maculopapular, or morbilliform patches and plaques on the trunk and extremities,
early involvement with erythema and peeling in the perineum/inguinal region may be an initial clue to the diagnosis. - Behçet Disease
multisystem disease that includes oral and genital ulceration and ocular disease (uveitis, relapsing iridocyclitis).
Recurrent aphthous stomatitis is present in almost all patients and is commonly the presenting symptom.
- Nine year old boy with cerebral palsy and seizures treated with carbamazepine. Seventeen days after start of therapy he demonstrated fever, rash (exanthematous), lymphadenopathy and nephritis, all part of a drug-induced hypersensitivity syndrome.
Medication Reactions
Most cutaneous reactions that result from the use of systemic medications are confined to the skin and resolve without sequelae after discontinuation of the offending agent
Moreseveredrugeruptionsmaybe life-threatening, making rapid recognition vital
Google: Acute generalised exanthematous pustulosis, or AGEP, is an uncommon pustular drug eruption characterised by superficial pustules.
AGEP is usually classified as a severe cutaneous adverse reaction (SCAR) to a prescribed drug. It is also called toxic pustuloderma.
Over 90% of cases of AGEP are provoked by medications, most often beta-lactam antibiotics (penicillins, cephalosporins and quinolones). Other drugs that may cause AGEP are reported to include:
Tetracyclines
Sulfonamides
Oral antifungals, particularly terbinafine
Calcium channel blockers such as diltiazem
Hydroxychloroquine
Carbamazepine
Paracetamol.
slide: * Acute generalized exanthematous pustulosis (AGEP) is a pustular lesion, often drug-related (aminopenicillins, macrolides, sulfonamides), that is characterized by many nonfollicular sterile pustules with underlying edema and erythema
Capillary Malformation (Port-Wine Stain)
Google
Capillary malformations (port wine stains or nevus flammeus, MIM #163000) are congenital low-flow vascular malformations of dermal capillaries and postcapillary venules. They are most often isolated skin anomalies but may rarely occur as part of complex malformation syndromes
- Port-wine stains are present at birth.
- These vascular malformations consist of mature dilated dermal capillaries.
- The lesions are macular, sharply circumscribed, pink to purple, and tremendously varied in size
- The head and neck region is the most common site of predilection; most lesions are unilateral.
- The mucous membranes can be involved. As a child matures into adulthood, the port-wine stain may become darker in color and pebbly in consistency; it may occasionally develop elevated areas that bleed spontaneously.
Cutis Marmorata Telangiectatica Congenita (Congenital Phlebectasia)
- Cutis marmorata telangiectatica congenita is benign vascular anomaly that represents dilatation of superficial capillaries and veins and is apparent at birth.
- Involved areas of skin have a reticulated red or purple hue that resembles physiologic cutis marmorata but is more pronounced and relatively unvarying
- CMTC affects males and females in equal numbers and is present at birth (congenital). Fewer than 300 cases of CMTC have been reported in the medical literature.
- Since many cases of CMTC are mild and clear up without treatment, the disorder may be under-diagnosed making it difficult to determine the true frequency of CMTC in the general population.
- The lesions may be restricted to a single limb and a portion of the trunk or may be more widespread.
- Port-wine stain may also be associated. The lesions become more pronounced during changes in environmental temperature, physical activity, or crying
Hemangioma
* Hemangiomas are proliferative hamartomas of vascular endothelium that may be present at birth or, more commonly, may become apparent in the 1st 2 mo of life, predictably enlarge, and then spontaneously involute.
* Hemangiomas are the most common tumor of infancy, occurring in 1-2% of newborns (higher in preterm infants) and 10% of white infants in the 1st year of life.
* Hemangiomas should be classified as superficial, deep, or mixed.
The terms strawberry and cavernous should not be used to describe
hemangiomas
* Superficial hemangiomas are bright red, protuberant, compressible, sharply demarcated lesions that may occur on any area of the body
Although sometimes present at birth, they more often appear in the 1st two months of life and are heralded by an erythematous or blue mark or an area of pallor, which subsequently develops a fine telangiectatic pattern before the phase of expansion
- A pyogenic granuloma is a small red, glistening, sessile, or pedunculated
- The surface may be weeping and crusted or completely epithelialized.
- Pyogenic granulomas initially grow rapidly, may ulcerate, and bleed easily when traumatized because they consist of exuberant granulation tissue.
- They are relatively common in children, particularly on the face, arms, and hands. Such a lesion located on a finger or hand may appear as a subcutaneous nodule.
- Pyogenic granulomas may arise at sites of injury, but a history of trauma often cannot be elicited.
- Clinically, they resemble and are often indistinguishable from small hemangiomas
Spider Angioma:
- A vascular spider (nevus araneus) consists of a central feeder artery with many dilated radiating vessels and a surrounding erythematous flush, varying from a few millimeters to several centimeters in diameter.
- Pressure over the central vessel causes blanching.
- Spider angiomas are associated with conditions in which there are increased levels of circulating estrogens, such as cirrhosis and pregnancy, but they also occur in up to 15% of normal preschool-aged children and 45% of school-aged children.
- Sites of predilection in children are the dorsum of the hand, forearm, face, and ears.
- Lesions often regress spontaneously after puberty.
- If removal is desired, laser is the mode of choice; resolution is achieved in 90% of cases with a single treatment.
Halo Nevus
- Halo nevi occur primarily in children and young adults, most commonly on the back
- Development of the lesion may coincide with puberty or pregnancy.
- Several pigmented nevi frequently develop halos simultaneously.
- Subsequent disappearance of the central nevus over several months is the usual outcome, and the depigmented area usually repigments
- Spitz nevus
Spitz nevus manifests most commonly in the 1st 2 decades of life as a pink to red, smooth, dome-shaped, firm, hairless papule on the face, shoulder, or upper limb
* Most are <1 cm in diameter, but they can achieve a size of 3 cm.
* Rarely, they occur as numerous grouped lesions.
* Visually similar lesions include pyogenic granuloma, hemangioma, nevocellular nevus, juvenile xanthogranuloma, and basal cell carcinoma,
but these entities are histologically distinguishable.
Café-Au-Lait Spots
* Café-au-lait spots are uniformly hyperpigmented, sharply demarcated macular lesions, the hues of which vary with the normal degree of pigmentation of the individual:
They are tan or light brown in white individuals and may be dark brown in black children
* Café-au-lait spots vary tremendously in size and may be large, covering a significant portion of the trunk or limb.
* Generally the borders are smooth, but some have exceedingly irregular borders.
* One to 3 café-au-lait spots are common in normal children; ≈ 10% of normal children have café-au-lait macules. The spots may be present at birth or may develop during childhood.
Tuberous Sclerosis
What is Tuberous Sclerosis? Tuberous sclerosis (also called tuberous sclerosis complex, or TSC) is a rare, multi-system genetic disease that causes non-cancerous (benign) tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.
What is Tuberous Sclerosis? Tuberous sclerosis (also called tuberous sclerosis complex, or TSC) is a rare, multi-system genetic disease that causes non-cancerous (benign) tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.
Atopic dermatitis
- Keratosis pilaris
Ggle: Keratosis pilaris is a common, mostly harmless skin condition that causes small, rough, white or reddish bumps or patches on the skin.
is a common papular eruption that may vary in extent from sparse lesions over the extensor aspects of the limbs to involvement of most of the body surface;
* Typical areas of involvement include the upper extensor surface of the arms and the thighs, cheeks, and buttocks.
* The lesions may resemble gooseflesh; they are noninflammatory, scaly, follicular papules that do not coalesce.
* Irritation of the follicular plugs occasionally causes erythema surrounding the keratotic papules
Pityriasis rosea
Pityriasis rosea is a self-limiting rash, which resolves in about 6–10 weeks. It is characterised by a large circular or oval “herald patch”, usually found on the chest, abdomen, or back.
The herald patch is followed some time later, typically two weeks or so, by the development of smaller scaly oval red patches, resembling a Christmas tree, distributed mainly on the chest and back.
Pityriasis rosea is most common in teenagers and young adults (10–35 year-olds), however it can affect people of any age
Occurs very slightly more often in women
Approximate incidence of 0.5% to 2%
Most cases occur in winter
Miliaria (Heat rash)
This type of miliaria occurs most frequently in newborn infants because of the relative immaturity and delayed patency of the sweat duct and the tendency for infants to be nursed in relatively warm, humid conditions.
Impetigo
Nonbullous impetigo accounts for > 70% of cases.
Impetigo starts as a red, itchy sore. As it heals, a crusty, yellow or “honey-colored” scab forms over the sore. In general, impetigo is a mild infection that can occur anywhere on the body. It most often affects exposed skin, such as. Around the nose and mouth.
Molluscum Contagiosum
Molluscum contagiosum is a fairly common skin infection caused by a virus. It causes round, firm, painless bumps ranging in size from a pinhead to a pencil eraser. If the bumps are scratched or injured, the infection can spread to nearby skin. Molluscum contagiosum also spreads through person-to-person contact and contact with infected objects.
Treat with Lemon Myrtle oil
