- Published on
Pathology - Hyperacute Rejection of Transplant
This irreversible type II hypersensitivity reaction of preformed recipient alloantibodies to either the ABO blood group or HLA class I antigens on the graft endothelium occurs within minutes to maybe hours. The binding of the antibodies promotes release of particles that promote coagulation and cytokines that recruit inflammatory mediators. The graft tissue is destroyed through vascular thrombosis and rapid organ death as described in this patient. It is now rare due to good ABO screening and HLA crossmatching.
Patients who are most prone to have this occur are often listed with the highest priority for a graft. Preformed antibodies may result from many transfusions, several pregnancies, or prior transplants.
This irreversible type II hypersensitivity reaction of preformed recipient alloantibodies to either the ABO blood group or HLA class I antigens on the graft endothelium occurs within minutes to maybe hours. The binding of the antibodies promotes release of particles that promote coagulation and cytokines that recruit inflammatory mediators. The graft tissue is destroyed through vascular thrombosis and rapid organ death as described in this patient. It is now rare due to good ABO screening and HLA crossmatching.
Patients who are most prone to have this occur are often listed with the highest priority for a graft. Preformed antibodies may result from many transfusions, several pregnancies, or prior transplants.
- Published on
Pathology - Graft Versus Host Disease
This reaction is a potential complication in bone marrow and liver transplants and is the result of T lymphocytes from donor transplant product perceiving the host tissues as foreign. The responding donor T cells activate CD4 + and CD8 + T cells in the host, inducing lymphocytic infiltration of the skin, GI tract, and liver. Damage to these organs creates the distinctive clinical signs including dermatitis, crampy stomach pain with bloody diarrhea and/or anorexia, cholestasis producing jaundice and probably hepatocellular necrosis, as well as fever. Severity of symptoms predicts mortality. The reaction may occur in days to weeks following transplant. Posttransplant immunosuppression and ways to eliminate T cells from donor tissue has lowered the incidence, although it is still relatively common. The conventional treatment consists of injectable glucocorticoids, which require careful tapering.
This reaction is a potential complication in bone marrow and liver transplants and is the result of T lymphocytes from donor transplant product perceiving the host tissues as foreign. The responding donor T cells activate CD4 + and CD8 + T cells in the host, inducing lymphocytic infiltration of the skin, GI tract, and liver. Damage to these organs creates the distinctive clinical signs including dermatitis, crampy stomach pain with bloody diarrhea and/or anorexia, cholestasis producing jaundice and probably hepatocellular necrosis, as well as fever. Severity of symptoms predicts mortality. The reaction may occur in days to weeks following transplant. Posttransplant immunosuppression and ways to eliminate T cells from donor tissue has lowered the incidence, although it is still relatively common. The conventional treatment consists of injectable glucocorticoids, which require careful tapering.
- Published on
Pathology - Pneumococcal Conjugate Vaccine in Sickle-Cell Disease
This patient may has functional asplenia secondary to splenic infarct from sickle-cell anemia. The objective of vignettes like this is to recognize what preventative measures are appropriate for certain patient groups. Patients with functional or surgical asplenia are at higher sensitivity to encapsulated pathogens such as pneumococcus. Although this patient should have had the pneumococcal conjugated vaccination, it is suggested that patients with asplenia additionally obtain the pneumococcal polysaccharide vaccine due to its extended number of serotypes covered. It is important to highlight that this patient is also sensitive to organisms such as Neisseria and Haemophilus . This patient should additionally receive the meningococcal and Haemophilus influenzae B vaccines if he has not already.
This patient may has functional asplenia secondary to splenic infarct from sickle-cell anemia. The objective of vignettes like this is to recognize what preventative measures are appropriate for certain patient groups. Patients with functional or surgical asplenia are at higher sensitivity to encapsulated pathogens such as pneumococcus. Although this patient should have had the pneumococcal conjugated vaccination, it is suggested that patients with asplenia additionally obtain the pneumococcal polysaccharide vaccine due to its extended number of serotypes covered. It is important to highlight that this patient is also sensitive to organisms such as Neisseria and Haemophilus . This patient should additionally receive the meningococcal and Haemophilus influenzae B vaccines if he has not already.
- Published on
Pathology - Wiskott - Aldrich Syndrome
Symptomatic triad of Wiskott–Aldrich syndrome (WAS) involves T hrombocytopenia, recurrent sinopulmonary I nfections, and E czema (mnemonic: TIE). WAS is an X-linked recessive disorder characterized by poor cell-mediated immunity and decreased IgM production through gradual deletion of T and B cells. The pathogenesis comes from a null-mutation in the gene that codes the WAS protein (WASP), a regulator of actin polymerization in hematopoietic cells. This leads in the absence of a particular glycoprotein receptor on T cells and platelets, resulting to a poor response to polysaccharide vaccines and to thrombocytopenia, respectively.
Megakaryocyte levels are typical. Splenomegaly can arise attributable to splenic sequestration of platelets, due to the faulty receptor and so contributing to the thrombocytopenia. Petechiae are small hemorrhages within the skin that are a sign of reduced platelets. Levels of IgG will be normal and IgA and IgE may be normal or elevated. Patients are prone to bacterial, viral, and fungal infections and also have a high frequency of autoimmune diseases and lymphoreticular cancers. Bone marrow transplantation may be useful as treatment.
Symptomatic triad of Wiskott–Aldrich syndrome (WAS) involves T hrombocytopenia, recurrent sinopulmonary I nfections, and E czema (mnemonic: TIE). WAS is an X-linked recessive disorder characterized by poor cell-mediated immunity and decreased IgM production through gradual deletion of T and B cells. The pathogenesis comes from a null-mutation in the gene that codes the WAS protein (WASP), a regulator of actin polymerization in hematopoietic cells. This leads in the absence of a particular glycoprotein receptor on T cells and platelets, resulting to a poor response to polysaccharide vaccines and to thrombocytopenia, respectively.
Megakaryocyte levels are typical. Splenomegaly can arise attributable to splenic sequestration of platelets, due to the faulty receptor and so contributing to the thrombocytopenia. Petechiae are small hemorrhages within the skin that are a sign of reduced platelets. Levels of IgG will be normal and IgA and IgE may be normal or elevated. Patients are prone to bacterial, viral, and fungal infections and also have a high frequency of autoimmune diseases and lymphoreticular cancers. Bone marrow transplantation may be useful as treatment.
- Published on
Pathology - Ataxia Telangiectasia Syndrome
Ataxia-telangiectasia syndrome is an autosomal recessive disorder stemming from a deficiency in DNA damage repair. Specifically, the ataxia-telangiectasia gene (ATM) is mutated. This gene encodes a protein, which normally serves as a regulator of cell-cycle checkpoints to give time for repair of double-stranded DNA breaks.
This abnormality results in deficient cellular immunity and humoral immunodeficiency with thymic hypoplasia due to the fragile chromosomes that are created within the cells. Instability of the chromosomes also puts patients at increased risk for lymphomas and leukemias. Patients will typically present after the first year of life, when they will be delayed in walking secondary to ataxia. The ataxia occurs subsequent to atrophy of the cerebellum, which normally functions to coordinate balance (in conjunction with the vestibular system) and fine motor control. Oculomotor apraxia, which is difficulties with coordinated head and eye movements, can appear as an inability to track objects in young children. Speech will likely also fail to develop adequately. Patients will exhibit characteristic ocular and cutaneous telangiectasias, which are dilated blood vessels. In addition to decreased IgE and IgA, they also interestingly have raised serum alpha-fetoprotein. Patients with Friedrich’s ataxia, which can present similarly, can be separated from ataxia-telangiectasia syndrome because those patients will not have signs of oculomotor apraxia or the immunologic abnormalities.
Ataxia-telangiectasia syndrome is an autosomal recessive disorder stemming from a deficiency in DNA damage repair. Specifically, the ataxia-telangiectasia gene (ATM) is mutated. This gene encodes a protein, which normally serves as a regulator of cell-cycle checkpoints to give time for repair of double-stranded DNA breaks.
This abnormality results in deficient cellular immunity and humoral immunodeficiency with thymic hypoplasia due to the fragile chromosomes that are created within the cells. Instability of the chromosomes also puts patients at increased risk for lymphomas and leukemias. Patients will typically present after the first year of life, when they will be delayed in walking secondary to ataxia. The ataxia occurs subsequent to atrophy of the cerebellum, which normally functions to coordinate balance (in conjunction with the vestibular system) and fine motor control. Oculomotor apraxia, which is difficulties with coordinated head and eye movements, can appear as an inability to track objects in young children. Speech will likely also fail to develop adequately. Patients will exhibit characteristic ocular and cutaneous telangiectasias, which are dilated blood vessels. In addition to decreased IgE and IgA, they also interestingly have raised serum alpha-fetoprotein. Patients with Friedrich’s ataxia, which can present similarly, can be separated from ataxia-telangiectasia syndrome because those patients will not have signs of oculomotor apraxia or the immunologic abnormalities.
- Published on
Pathology - DiGeorge Syndrome
congenital thymic aplasia is more often known as DiGeorge syndrome. The condition originates from a failure of the third and fourth pharyngeal pouches to form, resulting in absence of the thymus and parathyroid glands. CATCH-22 is a famous mnemonic used to memorize the clinical signs of the condition. The primary findings are connected to C ardiac defects, as suggested by this patient’s typical ventricular septal defect murmur, as well as A bnormal midline features, including the facial traits mentioned in this patient. Failure of T hymic development results in absence of T cells and susceptibility to opportunistic pathogens, particularly P. jirovecii . C left palate is also a common finding. The lack of PTH can generate symptomatic H ypocalcemia and tetany, as evidenced by the positive Trousseau’s sign (carpal and phalangeal spasm) when the blood pressure cuff is inflated on the patient. The normal genetic mutation is not inherited, but rather a random deletion of the long arm on chromosome 22 (22q11.2 deletion). Live vaccines (e.g., measles, small pox, varicella) are contraindicated. Presentation can be as severe as those of SCID. Therapy involves antimicrobial prophylaxis and thymic transplantation, however the risk of graft-versus-host disease (GVHD) is substantial.
congenital thymic aplasia is more often known as DiGeorge syndrome. The condition originates from a failure of the third and fourth pharyngeal pouches to form, resulting in absence of the thymus and parathyroid glands. CATCH-22 is a famous mnemonic used to memorize the clinical signs of the condition. The primary findings are connected to C ardiac defects, as suggested by this patient’s typical ventricular septal defect murmur, as well as A bnormal midline features, including the facial traits mentioned in this patient. Failure of T hymic development results in absence of T cells and susceptibility to opportunistic pathogens, particularly P. jirovecii . C left palate is also a common finding. The lack of PTH can generate symptomatic H ypocalcemia and tetany, as evidenced by the positive Trousseau’s sign (carpal and phalangeal spasm) when the blood pressure cuff is inflated on the patient. The normal genetic mutation is not inherited, but rather a random deletion of the long arm on chromosome 22 (22q11.2 deletion). Live vaccines (e.g., measles, small pox, varicella) are contraindicated. Presentation can be as severe as those of SCID. Therapy involves antimicrobial prophylaxis and thymic transplantation, however the risk of graft-versus-host disease (GVHD) is substantial.
- Published on
Pathology - Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) is an X-linked recessive condition. Like with other autoimmune disorders, the sorts of microorganisms that infect the patient hint to the deficiency in the immune response. A patient with CGD will have recurrent infections from fungus and staphylococcus (gram-positive cocci in clusters). The deficiency in CGD is inadequate nicotine adenine dinucleotide phosphate oxidase in neutrophil and monocyte cell membranes, resulting to suppressed superoxide dismutase activity and lowered hydrogen peroxide levels. This limits free-radical generation and resulting in an absence respiratory burst, such that phagocytized catalase-positive bacteria are not destroyed. The diagnosis of CGD can be made by the laboratory observation of neutrophils and macrophages failing to decrease a nitroblue tetrazolium dye (leukocytes with an intact respiratory burst create a blue color upon incubation). Myeloperoxidase deficiency, which is a more common abnormality, is characterized by a normal respiratory burst but absence of hypochlorous acid (bleach) synthesis. The only clinical importance, however, shows in vulnerable patients with DM through significant candidal infections.
Chronic granulomatous disease (CGD) is an X-linked recessive condition. Like with other autoimmune disorders, the sorts of microorganisms that infect the patient hint to the deficiency in the immune response. A patient with CGD will have recurrent infections from fungus and staphylococcus (gram-positive cocci in clusters). The deficiency in CGD is inadequate nicotine adenine dinucleotide phosphate oxidase in neutrophil and monocyte cell membranes, resulting to suppressed superoxide dismutase activity and lowered hydrogen peroxide levels. This limits free-radical generation and resulting in an absence respiratory burst, such that phagocytized catalase-positive bacteria are not destroyed. The diagnosis of CGD can be made by the laboratory observation of neutrophils and macrophages failing to decrease a nitroblue tetrazolium dye (leukocytes with an intact respiratory burst create a blue color upon incubation). Myeloperoxidase deficiency, which is a more common abnormality, is characterized by a normal respiratory burst but absence of hypochlorous acid (bleach) synthesis. The only clinical importance, however, shows in vulnerable patients with DM through significant candidal infections.
- Published on
Pathology - Leukocyte Adhesion Defect
Leukocyte adhesion defect is a rare autosomal recessive disorder that comes from mutations of either integrin-mediated leukocyte adhesion (β2 integrin subunit deficiency) or selectin-mediated leukocyte rolling. Thus, neutrophils are not able to connect to the endothelium and undergo diapedesis to reach affected tissues, hence patients are susceptible to bacterial and fungal infections. Significantly high amounts of blood leukocytes are discovered due to the inability of neutrophils to escape the blood arteries. Impaired wound healing with the absence of pus is characteristic.
A crucial discovery in this condition is delayed loss of the umbilical chord. Hematopoietic stem cell transplantation may be required in severe types. Currently, bone marrow transplantation is the only curative treatment, however gene therapy may be a possibility in the future.
Leukocyte adhesion defect is a rare autosomal recessive disorder that comes from mutations of either integrin-mediated leukocyte adhesion (β2 integrin subunit deficiency) or selectin-mediated leukocyte rolling. Thus, neutrophils are not able to connect to the endothelium and undergo diapedesis to reach affected tissues, hence patients are susceptible to bacterial and fungal infections. Significantly high amounts of blood leukocytes are discovered due to the inability of neutrophils to escape the blood arteries. Impaired wound healing with the absence of pus is characteristic.
A crucial discovery in this condition is delayed loss of the umbilical chord. Hematopoietic stem cell transplantation may be required in severe types. Currently, bone marrow transplantation is the only curative treatment, however gene therapy may be a possibility in the future.
- Published on
Pathology - C5 Deficiency
Disorder of the complement system specifically C5 deficiency, leading to bacterial meningitis from Neisseria meningitidis . Complement deficits can result in disruption of the traditional route (C1q, C1r, C1s, C2, and C4), which result in respiratory tract or tissue-invasive bacterial infections, usually by Streptococcus pneumoniae , and can culminate in septicemia. Defects in the alternative pathway (C5, C6, C7, C8, and C9) result in susceptibility to N. gonorrhoeae or N. meningitidis infections. In this example, the patient’s lethargy, fever, vomiting, headache, and positive Brudzinski’s sign (reflexive hip flexion with passive neck flexion) hint toward meningitis.
A petechial eruption is symptomatic of N. meningitidis infection and gram-negative diplococci in the CSF corroborate the diagnosis. Functional assays can examine the status of classic and alternative complement pathways, and determination of relative components status can provide a diagnosis. Rarely, a life-threatening and often deadly complication known as Waterhouse–Friderichsen syndrome can emerge due to bleeding within the adrenal glands attributable to N. meningitidis infection.
Disorder of the complement system specifically C5 deficiency, leading to bacterial meningitis from Neisseria meningitidis . Complement deficits can result in disruption of the traditional route (C1q, C1r, C1s, C2, and C4), which result in respiratory tract or tissue-invasive bacterial infections, usually by Streptococcus pneumoniae , and can culminate in septicemia. Defects in the alternative pathway (C5, C6, C7, C8, and C9) result in susceptibility to N. gonorrhoeae or N. meningitidis infections. In this example, the patient’s lethargy, fever, vomiting, headache, and positive Brudzinski’s sign (reflexive hip flexion with passive neck flexion) hint toward meningitis.
A petechial eruption is symptomatic of N. meningitidis infection and gram-negative diplococci in the CSF corroborate the diagnosis. Functional assays can examine the status of classic and alternative complement pathways, and determination of relative components status can provide a diagnosis. Rarely, a life-threatening and often deadly complication known as Waterhouse–Friderichsen syndrome can emerge due to bleeding within the adrenal glands attributable to N. meningitidis infection.
- Published on
Pathology - Systemic Lupus Erythematosus
systemic lupus erythematosus (SLE) is an inflammatory autoimmune illness that affects numerous organ systems. The most common manifestations are skin rashes (as this patient’s characteristic malar butterfly rash), joint pains, and constitutional symptoms; however, renal, cardiac, pulmonary, and neurologic sequelae are also common (mnemonic – SOAP BRAIN MD: serositis, oral ulcers, arthritis, photosensitivity, blood disorders, renal dysfunction, ANA positive, immunologic phenomena, neurologic symptoms, malar rash and discoid rash). It is significantly more common in females and incidence is higher in the African American community. The pathogenesis of SLE likely starts with interaction of susceptibility genes and environmental variables resulting in aberrant immune responses.
Immune responses, which may differ between patients, result in the formation of antigens, autoantibodies and immune complexes (type III hypersensitivity response), which circulate and deposit in tissue, resulting in inflammatory processes and damage to multisystem organs. The presence of ANA is frequent in virtually all patients with SLE, but not specific for SLE. However, follow-up testing for anti-dsDNA or anti-Smith antibodies (anti-Sm) is specific for SLE and confirms the diagnosis. The most common cardiac symptom is pericarditis, which responds favorably to NSAIDs.
Headaches are very prevalent and periods of psychosis can occasionally occur, but must be separated from glucocorticoidinduced psychosis as immunosuppression is a cornerstone of care of SLE. Diffuse proliferative glomerulonephritis is the most prevalent renal manifestation and the major cause of morbidity and mortality. Anticardiolipin antibodies may also be present and will generate a false-positive in syphilis screening.
systemic lupus erythematosus (SLE) is an inflammatory autoimmune illness that affects numerous organ systems. The most common manifestations are skin rashes (as this patient’s characteristic malar butterfly rash), joint pains, and constitutional symptoms; however, renal, cardiac, pulmonary, and neurologic sequelae are also common (mnemonic – SOAP BRAIN MD: serositis, oral ulcers, arthritis, photosensitivity, blood disorders, renal dysfunction, ANA positive, immunologic phenomena, neurologic symptoms, malar rash and discoid rash). It is significantly more common in females and incidence is higher in the African American community. The pathogenesis of SLE likely starts with interaction of susceptibility genes and environmental variables resulting in aberrant immune responses.
Immune responses, which may differ between patients, result in the formation of antigens, autoantibodies and immune complexes (type III hypersensitivity response), which circulate and deposit in tissue, resulting in inflammatory processes and damage to multisystem organs. The presence of ANA is frequent in virtually all patients with SLE, but not specific for SLE. However, follow-up testing for anti-dsDNA or anti-Smith antibodies (anti-Sm) is specific for SLE and confirms the diagnosis. The most common cardiac symptom is pericarditis, which responds favorably to NSAIDs.
Headaches are very prevalent and periods of psychosis can occasionally occur, but must be separated from glucocorticoidinduced psychosis as immunosuppression is a cornerstone of care of SLE. Diffuse proliferative glomerulonephritis is the most prevalent renal manifestation and the major cause of morbidity and mortality. Anticardiolipin antibodies may also be present and will generate a false-positive in syphilis screening.
