Primary Immunodeficiency Disorders: Session Guide PDF

2/17/25, 10:06 PM OneNote Note the melanin pigment The stem cells of the ma...

2/17/25, 10:06 PM OneNote Note the melanin pigment The stem cells of the ma transferred from the bulbar the root of the nail, and melanocytes residing in the keratin of the nail. Nail k hair matrix to the cortex (C) the hair cortex. and the medulla (M) of the hair shaft. The cross section of the hair follicle is at the level of the follicular bulge (FB) which is a protrusion of the external root sheath (ERS) Session Guide: A-6-3: Immunodeficiency Lab (Classroom-based iLab) Tuesday, 02/18/2025 at 3:00 PM - 4:50 PM Assignment Info for Students (if none, leave blank) Submission Instructions, Due Date, and Time Graded-Yes or No Osmosis Playlist https://www.osmosis.org/playlist/QCcwG0rwtlb RAP Educational Objectives Session Objective RAP Educational Objectives Answer # Assigned Student 03-12508 Describe the association of dermatologic findings with certain primary Primary Immunodeficiency Disorders (PIDs) are exactly as the name states, Emma Rohrs immunodeficiencies. Technically PIDs can manifest in any organ system but the focus of this articl general this article is emphasizing that some common skin conditions such a infections might be a sign of a primary immunodeficiency disorder. The artic are extensive, recurrent, are not responding to therapy, or if there are other investigation into a possible PID should be done. A lot of these conditions ari to catch them early (and dermatologists can play an important part in this)! I would say the main take away is that the following derm conditions are ass Eczema Erythroderma Viral warts or molluscum contagiosum Chronic mucocutaneous candidiasis Recurrent non-healing ulcers Skin abscesses Petechial or purpuric spots And to cover this objective thoroughly here are the details on what specific P Eczema - Various PIDS Many PIDs have eczema as a clinical manifestation Wiskott-Aldrich Syndrome (WAS) photos: https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 22/28 2/17/25, 10:06 PM OneNote Chronic Mucocutaneous Candidiasis as a Predominant Manifestation in PID Candida infection localized to skin and mucous membranes PIDs involving both innate and adaptive can have CMC as a predomina This table summarizes each of the PIDs and denotes their clinical featu Molluscum Contagiosum as a result of PIDS: Viral infection ○ Poxvirus family Discrete papular or nodular lesions PIDs that predispose to molluscum contagiosum ○ WAS ○ AR-HIES (DOCK8 mutation) Warts as a result of PIDs: HPV (human papilloma virus) ○ Infect skin and mucosa ○ Cutaneous and genital warts Cellular immunity (T helper cells and NK cells) typically defend against Associated with many PIDs predispose to warts ○ PID should be suspected if recurrent warts, warts resistant to the https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 23/28 2/17/25, 10:06 PM OneNote *They stopped having a nice table at this point so I tried my best to conden likely important for us to know right now! Dermatologic findings are highlig Cutaneous Granuloma - list of PIDs: Common Variable Immunodeficiency (CVID) ○ Variable clinical phenotype ○ Appear in 2nd to 3rd decade of life ○ Vitiligo ○ Psoriasis ○ Granulomatous lesions Chronic Granulomatus Disease (CGD) ○ Deep-seated abscesses Staph aureus and candida spp. Single or multiple cutaneous scars Blau Syndrome ○ Triad Granulomatous arthritis Uveitis Rash Erythematous Fine Maculopapular Scaling Misdiagnosed as eczema Leukocyte adhesion defect: Rare PID Defect in migration of neutrophils at infection sites No pus formation at sites of infection because no neutrophils or mono ○ Non-healing skin ulcers ○ Pyoderma gangrenosum lesions Papillon-Lefevre Syndrome: AR disorder Mutation in cathepsin C gene Palmoplantar hyperkeratosis ○ Ages 1-4 Periodontitis Inflamed gingiva Severe combined Immunodeficiency (SCID): First 6 months of life Bacterial, viral and fungal infections Pneumonia, diarrhea, otitis media, sepsis, oral thrush, meningitis Irradiated blood infusion = erythematous maculopapular rash ○ Scaling and alopecia Omen Syndrome (subtype of SCID) ○ Persistent elevated activated and abnormal T lymphocytes Scaling and erythematous rash and alopecia https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 24/28 2/17/25, 10:06 PM OneNote PIDs that present with hypopigmentation of skin/hair: Griscelli syndrome Type II ○ Albinism and silver hair ○ Mutation in REB27A gene ○ Hemophagocytic lymph histiocytosis (HLH) Chediak Higashi Syndrome ○ LYST mutation ○ Hypopigmented skin and hair ○ HLH ○ Peripheral neuropathy and intellectual disability Hermansky Pudlak Syndrome ○ Albinism and bleeding tendency ○ Defect in platelet dense granules ○ 9 different subtypes Familial Mediterranean Fever: Erysipelas like erythema ○ Distal extremities (foot and ankles) Tumor necrosis factor receptor associated periodic fever syndrome (TRAPS Erythematous rash that starts on trunk and migrates distally Subcutaneous swelling and periorbital edema Cryopyrin associated periodic fever syndrome: Urticaria like rash Periodic fever syndrome Enlargement of long bones Rash in Deficiency of IL-1 Receptor Antagonist (DIRA): Grouping of pustules Neutrophilic pustules Onset during neonatal period Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated t Systemic inflammation Skin lesions over areas exposed to cold ○ Nose, pinna, distal extremities ○ Violaceous nodular/plaque lesions, general pustules, livedo retic Autoinflammation with phospholipase associated antibody deficiency and Blistering skin lesions Cold urticarial Cutaneous granulomas Bronchiolitis Inflammation in eyes 03-12509 Identify which children should be evaluated for a primary immunodeficiency. A family history of primary immunodeficiency disease is the strongest p Brigid O'Brien disease The most common presentations of a primary immunodeficiency disease pulmonary infections, diarrhea and failure to thrive In the US, the common primary immunodeficiency diseases (from most to combined B-cell and T-cell disorders, phagocytic defects and complemen In general, children with PIDs develop infections more frequently, more s https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 25/28 2/17/25, 10:06 PM OneNote ○ Have bacterial or fungal infections with unusual organisms, or unus with common organisms If an immunodeficiency disease is suspected, initial lab screening should i and measurement of immunoglobin and complement levels ○ Lymphocytopenia (low WBCs) → T-cell disorder ○ Neutropenia (low neutrophils) → phagocytic disorder ○ Abnormal serum immunoglobin levels → B-cell disorder ○ Abnormalities on assay of classic or alternative pathways → comple 03-4690 Describe the main differences between primary and secondary Primary Immunodeficiencies: are caused by inherited defects of either no Pano Gentis immunodeficiencies immune defenses. Susceptibility can become apparent shortly after birth or whereas other patients develop symptoms later in life. Below are some exam that were given in the textbook. complement deficiencies (ex. Hereditary angioedema) leukocyte adhesion deficiencies chronic granulomatous disease X-linked agammaglobulinemia hyper IgM syndrome selective IgA deficiency (most common inherited form of immunoglob severe combined immunodeficiency disease (SCID) Secondary Immunodeficiencies: occur as a result of an acquired impairm both. Systemic disorders such as diabetes mellitus, malnutrition, hepatitis Immunosuppressive treatments such as cytotoxic chemotherapy, bone transplantation, or radiation therapy Prolonged critical illness due to infection, surgery, or trauma in the very Extensive burns, that will determine a loss of the skin barrier Splenectomy, removal of the spleen due to injury Unlike primary immunodeficiencies, which have a genetic basis, secondary im if the underlying cause is resolved. Patients with secondary immunodeficienc to an otherwise benign infection by opportunistic pathogens 03-4691 Enumerate causes of secondary immunodeficiencies Secondary immunodeficiency - occurs as a result of an acquired impairment Nick Nakasian both. Unlike primary immunodeficiencies, these can be reversible if the unde with secondary immunodeficiencies develop an increased susceptibility to ot opportunistic pathogens (example given: Candida spp., P. jirovecii, and Cryp Causes of secondary immunodeficiencies include disease, diet, or environm Systemic disorders - diabetes mellitus, malnutrition, hepatitis, or HIV/ Immunosuppressive treatments - cytotoxic chemotherapy, bone marr radiation therapy, immunosuppressive drugs Prolonged critical illness due to infection, surgery, or trauma in the ver patients Extensive burns - loss of the skin barrier Splenectomy - removal of the spleen due to injury Zinc deficiency - impairs T cell and DC function and reduces the killing Aging – thymus involution (no more new T cells), protein loss *Most common cause of secondary immunodeficiency - Malnutrition (I guess enumerate just means "list", Sarah's starred objective 4701 explains Session Objectives Session Objective # Session Objectives Facilitator Notes Readi 4700 * Describe the immunopathology of the following primary Overall due to genetic defects. Me Chris Chia immunodeficiencies (complement deficiency, leukocyte complement deficiency: join co adhesion deficiency, CGD, SCID, selective IgA deficiency, -Hereditary angioedema is most common complement immune agammaglobulinemias). deficiency. C1 inhibition -uncontrolled and spontaneous inflammatory reactions -C4 and C2 Lectin pathway affected https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 26/28 2/17/25, 10:06 PM OneNote -Deficiencies in C3 Generalized infections -unable to opsonize -C5-9 -recurrent meningitis especially from Neisseria from defective membrane attack complex Leukocyte adhesion deficiency, -impaired leukocyte adhesion to the endothelium CGD -Deficient NADPH oxidase in neutrophils and macrophages -decreases antibacterial ability -X-linked -susceptible to many bugs and fungi so need prophylaxis antibacterials and antifungals SCID -B cells and T cells defect impairing T-cell dependent antibody response (no adaptive activation) -Vaccines are ineffective -highly susceptible to opportunistic infections: Candida, Pneumocystis Jirovecii or Ecoli -if developed in first few months, usually diagnostic of SCIDs. -Bone marrow transplant possible, but latent viruses pose lethal threat selective IgA deficiency, -inability to produce secretory IgA (no mucus antibodies) -High prevalence of GI and respiratory infections -1/800 Agammaglobulinemias -Generally lead to inability of B-Cell to not produce a specific type of antibody- x-linked -Burton X-linked Agammaglobulinemia (XLA) -Lacking gene for Bruton Tyrosine Kinase -B-cells stuck as "pre-B-Stage" -X-linked Hyper IgM syndrome -Defective CD40L preventing class switching of Igs so all are stuck as IgM 4701 * Describe secondary immunodeficiency conditions (except These are the examples discussed in the textbook. I will update if Me Sarah Shelley HIV) we discuss additional details/examples in class! join co (Do no Secondary Immunodeficiency Conditions: Acquired through disease, diet, or environmental exposures. Occurs as a result of an acquired impairment of the function of B cells, T cells, or both. Often reversible if the underlying cause is resolved. Malnutrition (most common cause worldwide): Affects both innate and adaptive immunity Reduction in protein synthesis which provokes a reduction in phagocyte function, complement and antibody synthesis, and cell- mediated immunity. Deficiency of vitamins and minerals affects the immune response - zinc deficiency impairs T cell and DC function and reduces the killing functions of phagocytes. Splenectomized patients: Removal of the spleen increases susceptibility to bacteremias with encapsulated bacteria, since specialized B cells (T-independent) in the spleen are crucial for mounting antibody responses to polysaccharide antigens carried in the capsule of some bacteria. Macrophages present in the spleen collaborate in eliminating microbial antigens from circulation via phagocytosis. Cancer patients: Suffer from immunosuppression Anti-proliferative/cytotoxic chemotherapy or radiation can cause death of bone marrow stem cells and inhibition of peripheral lymphocyte proliferation. The immune system could be the origin of the cancer cells (e.g. leukemias or lymphomas) which would lead to the disruption of normal output of immune cells from the bone marrow, crowding of https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 27/28 2/17/25, 10:06 PM OneNote lymphoid organs due to leukocyte proliferation, or loss of normal antibody responses. Patients taking immunosuppressant drugs: Patients who are receiving treatment for inflammatory conditions or controlling transplant rejection. Example: corticosteroids exert a broad inhibition of cytokine gene expression, phagocyte migration, and lymphocyte function. Specific drugs: cyclosporine or anti-CD3 serum - used in transplant rejection. Target specific immune populations. May inhibit or eliminate T cells. Aging Involution of thymus - by age 40 humans stop producing new T cells Decrease in output of immune cells by bone marrow Low degree of chronic inflammation in the elderly which alters the capacity of the immune system to fight infections Protein loss: Can cause low antibody levels, hypoproteinemia, or Crohn's disease. Extensive burns Loss of skin immune barrier functions Diabetes Decrease in the overall immune response of the patient https://catmailohio-my.sharepoint.com/personal/cw427624_ohio_edu/_layouts/15/Doc.aspx?sourcedoc={434df08f-0ff3-4dc1-9da7-6963d7f38995}&a… 28/28