Epidemiology and Etiology

Epidemiology

• Equally identified in all ethnicities and races
• EstimatedincidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency: approximately 1 case per 200,000 live births per year
• Predominant in males (65%–70% of cases are from anX-linkedX-linkedGenetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases.Common Variable Immunodeficiency (CVID)mutationMutationGenetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations.Types of Mutations)
• MortalityMortalityAll deaths reported in a given population.Measures of Health Status:
  • MostpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship now survive until 30–40 years of age.
  • MortalityMortalityAll deaths reported in a given population.Measures of Health Status elevated after age > 10 years
  • X-linkedX-linkedGenetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases.Common Variable Immunodeficiency (CVID) form of the disease is associated with the highestmortalityMortalityAll deaths reported in a given population.Measures of Health Status andmorbidityMorbidityThe proportion of patients with a particular disease during a given year per given unit of population.Measures of Health Status.

Etiology

Chronicgranulomatous diseaseGranulomatous diseaseA defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern.Common Variable Immunodeficiency (CVID) (CGD) is caused by mutations in thegenesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure encoding forproteinsProteinsLinear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein.Energy Homeostasis that make up thenicotinamide adenine dinucleotideNicotinamide adenine dinucleotideA coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH).Pentose Phosphate PathwayphosphatePhosphateInorganic salts of phosphoric acid.Electrolytes (NADPHNADPHNicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5′-phosphate (nmn) coupled by pyrophosphate linkage to the 5′-phosphate adenosine 2.Pentose Phosphate Pathway)oxidaseOxidaseNeisseria: 

• Gp91phox (X-linkedX-linkedGenetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases.Common Variable Immunodeficiency (CVID) disorder)
• P47phox (NCF1geneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics found onchromosomeChromosomeIn a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.Basic Terms of Genetics 7, autosomal inheritance)
• P22phox (autosomal recessiveAutosomal recessiveAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited.Autosomal Recessive and Autosomal Dominant Inheritance)
• P67phox (autosomal recessiveAutosomal recessiveAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited.Autosomal Recessive and Autosomal Dominant Inheritance)
• P40phox (autosomal recessiveAutosomal recessiveAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited.Autosomal Recessive and Autosomal Dominant Inheritance)

Pathophysiology

NormalphagocytosisPhagocytosisThe engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes).Innate Immunity: Phagocytes and Antigen Presentation pathway

• NeutrophilsNeutrophilsGranular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Innate Immunity: Phagocytes and Antigen Presentation phagocytosebacteriaBacteriaBacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases.Bacteriology and other pathogens
• ↑ Oxygen consumption 
• Produce different reactive oxidant species, which arebactericidalBactericidalPenicillins 

Pathophysiology of CGD

The NADPH-oxidase enzyme is impaired in phagocytic cell → ↓ production of superoxide anion O₂^–, which affects other oxidants. This enzyme is responsible for the inability to fight infections.

• Catalase-positive microorganisms are implicated in life-threatening infections:
  • BurkholderiaBurkholderiaBurkholderia species are gram-negative bacilli with 2 clinically relevant pathogens: B. pseudomallei (causing melioidosis) and B. cepacia complex (causing opportunistic infections). Melioidosis is commonly seen in Asia and Australia. Infection is transmitted by contact with contaminated soil or water (via skin wounds).Burkholderia cepacia
  • AspergillusAspergillusA genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae.Echinocandins
  • Candida albicansCandida albicansA unicellular budding fungus which is the principal pathogenic species causing candidiasis (moniliasis).Candida/Candidiasis
  • Staphylococcus aureusStaphylococcus aureusPotentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Brain Abscess
  • NocardiaNocardiaNocardia is a branching, filamentous, gram-positive bacilli. It is partially acid fast due to the presence of mycolic acids in the cell wall. Nocardia is a ubiquitous soil organism that most commonly affects immunocompromised patients. Nocardia is transmitted via inhalation of aerosolized bacteria or less commonly, via direct contact with wounds.Nocardia/Nocardiosisspp.
  • Serratia marcescensSerratia MarcescensA species of gram-negative, facultatively anaerobic, rod-shaped bacteria found in soil, water, food, and clinical specimens. It is a prominent opportunistic pathogen for hospitalized patients.Aminoglycosides
• AlthoughPseudomonas aeruginosaPseudomonas aeruginosaA species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection.Pseudomonas is catalase-positive, it is killed byneutrophilsNeutrophilsGranular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Innate Immunity: Phagocytes and Antigen Presentation in CGDpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship.
• Catalase-negative microorganisms can still be killed by phagocytes.

Clinical Presentation

General presentation

Most CGDpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship are < 5 years of age, and the severity isvariableVariableVariables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups.Types of Variables (depending on thegenetic defectGenetic DefectIon Channel Myopathy). Clinical presentation can include:

• Growth failure
• Abnormalwound healingWound healingWound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling.Wound Healing
• Infections

Infections

PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship may experience repeated infections caused by bacterial and fungal pathogens.

• PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship can exhibit few clinical symptoms and signs despite the severity of infection
• Viral infection response is normal
• An infectious etiology should always be searched for in any child presenting with afeverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin.Fever.
• Types of infections include:
  • PneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia
  • Abscesses (perianal, perirectal,liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy)
  • Suppurative adenitis
  • OsteomyelitisOsteomyelitisOsteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus.Osteomyelitis
  • BacteremiaBacteremiaThe presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion.Glycopeptides/fungemia
  • SuperficialskinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions infections (cellulitisCellulitisCellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness.Cellulitis/impetigoImpetigoImpetigo is a highly contagious superficial bacterial infection typically caused by Staphylococcus aureus (most common) and Streptococcus pyogenes. Impetigo most commonly presents in children aged 2 to 5 years with lesions that evolve from papules to vesicles to pustules, which eventually break down to form characteristic “honey-colored” crusts.Impetigo)

Inflammatory and other manifestations

• Granulomata: mostly in GI and genitourinary tracts
• GI manifestations:
  • Inflammatory bowel disease (IBD)
  • DiarrheaDiarrheaDiarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation.Diarrhea 
  • ColitisColitisInflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever.Pseudomembranous Colitis
  • Proctitis
  • Fistulae 
  • VomitingVomitingThe forcible expulsion of the contents of the stomach through the mouth.Hypokalemia
  • ConstipationConstipationConstipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency< 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic.Constipation
• Hepatic:
  • ElevatedliverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: AnatomyenzymesEnzymesEnzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules.Basics of Enzymes
  • Hepatitis
  • LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy abscesses 
  • Portal hypertensionPortal hypertensionPortal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome.Portal Hypertension
• Ophthalmic:
  • Chorioretinal lesions (mostlyX-linkedX-linkedGenetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases.Common Variable Immunodeficiency (CVID) CGD)
• Pulmonary:
  • BronchiectasisBronchiectasisBronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections.Bronchiectasis
  • ChronicfibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans

Diagnosis

General evaluation

• HypergammaglobulinemiaHypergammaglobulinemiaAn excess of gamma-globulins in the serum due to chronic infections or paraproteinemias.Autoimmune Hepatitis →chronic inflammationChronic InflammationInflammation
• ↓ CirculatingB cellsB cellsLymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.B cells: Types and Functions
• CD4 T-cell lymphocytopenia
• AnemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology.Anemia: Overview and Types of chronic disease
• ↑ Markers ofinflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function.Inflammation (erythrocyte sedimentation rateErythrocyte Sedimentation RateSoft Tissue Abscess (ESRESRSoft Tissue Abscess) and CRP)
• HypoalbuminemiaHypoalbuminemiaA condition in which albumin level in blood (serum albumin) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (albuminuria).Nephrotic Syndrome in Children
• Imaging studies are dictated according to the presenting infectious process.

Specific laboratory evaluation

Neutrophil function tests should be done:

• Nitroblue tetrazolium test: normal phagocytes reduce NBT to blue formazan 
• Dihydrorhodamine (DHR) test:
  • More accurate than nitroblue tetrazolium test for the diagnosis of CGD
  • DHR results: phagocytes are unable to ↓ DHR in the fluorescent active compound, rhodamine
  • The extent of conversion varies based on the geneticmutationMutationGenetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations.Types of Mutations.

Moleculargenetic testingGenetic TestingDetection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Myotonic Dystrophies andgenotypingGenotypingMethods used to determine individuals’ specific alleles or snps (single nucleotide polymorphisms).Polymerase Chain Reaction (PCR):

• Indicated in familial cases of CGD
• Can be used on chorionic villus sampling for previously identified mutations

BiopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma

• Performed whengranulomasGranulomasA relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.Sarcoidosis form
• Histologic examination:
  • Necrotic centers
  • Layers of histiocytes andmacrophagesMacrophagesThe relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells.Innate Immunity: Phagocytes and Antigen Presentation

Management

• Hematopoietic stem cell transplantationHematopoietic stem cell transplantationTransfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms.Organ Transplantation from a HLA-compatible donor
• AntimicrobialprophylaxisProphylaxisCephalosporins (trimethoprimTrimethoprimThe sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect.Sulfonamides and Trimethoprim–sulfamethoxazoleSulfamethoxazoleA bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance.Sulfonamides and Trimethoprim is considered 1st-line treatment)
• Aggressive treatment of current infections
  • SkinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions infections: IVciprofloxacinCiprofloxacinA broad-spectrum antimicrobial carboxyfluoroquinoline.Fluoroquinolones
  • FungalpneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia:voriconazoleVoriconazoleA triazole antifungal agent that specifically inhibits sterol 14-alpha-demethylase and cytochrome p-450 cyp3a.Azoles orposaconazolePosaconazoleAzoles for up to 6 months
• Administration of interferon-gamma
• Surgical drainage of abscesses
• GeneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics therapy is undergoing extensiveresearchResearchCritical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws.Conflict of Interest and development.

Differential Diagnosis

• CysticCysticFibrocystic ChangefibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans (CF):autosomal recessiveAutosomal recessiveAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited.Autosomal Recessive and Autosomal Dominant Inheritance disorder. MostcarriersCarriersThe Cell: Cell Membrane of the CFgeneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics are asymptomatic, and the disease manifests as an exocrine gland dysfunction that involves multiple organ systems but usually results in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications in untreatedpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship.Pulmonary involvementPulmonary involvementCoccidioides/Coccidioidomycosis occurs in 90% ofpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship who survive the neonatal period. End-stage lung disease is the principal cause of death
• Hyperimmunoglobulin E syndrome (HIES): first described as Job syndrome in 1966. Hyperimmunoglobulin E syndrome is characterized by recurrentskinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions abscesses, recurrentpneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia with pneumatocele, eczematousdermatitisDermatitisAny inflammation of the skin.Atopic Dermatitis (Eczema), and elevated serumIgEIgEAn immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity.Immunoglobulins: Types and Functions levels. HIES was initially reported to have anautosomal dominant inheritanceAutosomal dominant inheritanceAutosomal Recessive and Autosomal Dominant Inheritance pattern, but cases withautosomal recessive inheritanceAutosomal recessive inheritanceAutosomal Recessive and Autosomal Dominant Inheritance andsporadicSporadicSelective IgA Deficiency cases have been reported
• Crohn’s disease (inpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship withinflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function.Inflammation limited to therectumRectumThe rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters.Rectum and Anal Canal: Anatomy):idiopathicIdiopathicDermatomyositis, chronic regionalenteritisEnteritisInflammation of any segment of the small intestine.Lactose Intolerance that most commonly affects the terminalileumIleumThe distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine.Small Intestine: Anatomy but has the potential to affect any part of the GI tract from mouth to anus. CD is defined bytransmural inflammationTransmural inflammationCrohn Disease that lacks continuity along the intestine (skip areas). In some cases, CD has nonnecrotizinggranulomasGranulomasA relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.Sarcoidosis containing epithelioid histiocytes.PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship present with typical signs of CD includingabdominal painAbdominal PainAcute Abdomen,bloody diarrheaBloody diarrheaDiarrhea, and in severe cases by intestinal fistulas, intramural abscesses, andbowel obstructionBowel obstructionAny impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal.Ascaris/Ascariasis.

References

1. Zerbe CS, Marciano BE, Holland SM. (2023). Chronic granulomatous disease: pathogenesis, clinical manifestations, and diagnosis. UpToDate. Retrieved November 6, 2024, fromhttps://www.uptodate.com/contents/chronic-granulomatous-disease-pathogenesis-clinical-manifestations-and-diagnosis
2. Marciano BE, Zerbe CS, Holland SM. (2023). Chronic granulomatous disease: Treatment and prognosis. UpToDate. Retrieved November 6, 2024, fromhttps://www.uptodate.com/contents/chronic-granulomatous-disease-treatment-and-prognosis
3. Nowicki RJ. (2019). Chronic Granulomatous Disease. eMedicine. Retrieved November 6, 2024, fromhttps://emedicine.medscape.com/article/1116022
4. Fischer, A. (2018). Primary Immune Deficiency Diseases. In Jameson JL, et al. (Ed.),Harrison’s Principles of Internal Medicine (20th ed., ch. 344).